chr22-50526017-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001953.5(TYMP):c.1284T>A(p.Gly428Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,470,092 control chromosomes in the GnomAD database, including 10,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G428G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.14 ( 1824 hom., cov: 34)

Exomes 𝑓: 0.11 ( 8393 hom. )

Consequence

TYMP
NM_001953.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.412

Publications

19 publications found

Variant links:

Genes affected

TYMP (HGNC:3148): (thymidine phosphorylase) This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2012]

TYMP links:

SCO2 (HGNC:10604): (synthesis of cytochrome C oxidase 2) Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. Human COX is a multimeric protein complex that requires several assembly factors; this gene encodes one of the COX assembly factors. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6. [provided by RefSeq, Oct 2014]

SCO2 Gene-Disease associations (from GenCC):

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
myopia 6
Inheritance: AD Classification: STRONG Submitted by: G2P
autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SCO2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 22-50526017-A-T is Benign according to our data. Variant chr22-50526017-A-T is described in ClinVar as Benign. ClinVar VariationId is 137876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.412 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYMP	NM_001953.5 link	c.1284T>A	p.Gly428Gly	synonymous_variant	Exon 9 of 10	ENST00000252029.8	NP_001944.1	P19971-1E5KRG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYMP	ENST00000252029.8 link	c.1284T>A	p.Gly428Gly	synonymous_variant	Exon 9 of 10	1	NM_001953.5	ENSP00000252029.3		P19971-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21351

AN:

151770

Hom.:

1819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0937

Gnomad EAS

AF:

0.0971

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.0469

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.112

AC:

8689

AN:

77894

AF XY:

0.117

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.0817

Gnomad FIN exome

AF:

0.0480

Gnomad NFE exome

AF:

0.0969

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.108

AC:

142497

AN:

1318212

Hom.:

8393

Cov.:

AF XY:

0.110

AC XY:

71220

AN XY:

650016

show subpopulations

African (AFR)

AF:

0.241

AC:

6351

AN:

26322

American (AMR)

AF:

0.124

AC:

3306

AN:

26564

Ashkenazi Jewish (ASJ)

AF:

0.0955

AC:

2190

AN:

22926

East Asian (EAS)

AF:

0.108

AC:

3102

AN:

28846

South Asian (SAS)

AF:

0.172

AC:

12463

AN:

72368

European-Finnish (FIN)

AF:

0.0530

AC:

1742

AN:

32898

Middle Eastern (MID)

AF:

0.112

AC:

441

AN:

3954

European-Non Finnish (NFE)

AF:

0.102

AC:

106562

AN:

1049736

Other (OTH)

AF:

0.116

AC:

6340

AN:

54598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6584

13169

19753

26338

32922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4190

8380

12570

16760

20950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.141

AC:

21372

AN:

151880

Hom.:

1824

Cov.:

AF XY:

0.140

AC XY:

10371

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.231

AC:

9558

AN:

41428

American (AMR)

AF:

0.160

AC:

2436

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0937

AC:

325

AN:

3470

East Asian (EAS)

AF:

0.0972

AC:

500

AN:

5146

South Asian (SAS)

AF:

0.177

AC:

853

AN:

4820

European-Finnish (FIN)

AF:

0.0469

AC:

495

AN:

10550

Middle Eastern (MID)

AF:

0.0993

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.101

AC:

6879

AN:

67886

Other (OTH)

AF:

0.134

AC:

282

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

948

1896

2845

3793

4741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

179

Bravo

AF:

0.151

Asia WGS

AF:

0.155

AC:

532

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Apr 23, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 23, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mitochondrial DNA depletion syndrome 1

Benign:2

Jan 14, 2016

GeneReviews

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mitochondrial neurogastrointestinal encephalomyopathy

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mitochondrial complex IV deficiency, nuclear type 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.1

(source)

DANN

Benign

0.67

PhyloP100

-0.41

PromoterAI

0.022

Neutral

(source)

Mutation Taster

=296/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over