rs786205098

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP3

The ENST00000252029.8(TYMP):c.1193_1198delCGCTGG(p.Ala398_Leu399del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,489,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TYMP
ENST00000252029.8 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 2.85

Publications

0 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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-50526102-ACCAGCG-A is Pathogenic according to our data. Variant chr22-50526102-ACCAGCG-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 16659.Status of the report is criteria_provided_single_submitter, 1 stars.

BP3

Nonframeshift variant in repetitive region in ENST00000252029.8

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252029.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TYMP	NM_001953.5	MANE Select	c.1193_1198delCGCTGG	p.Ala398_Leu399del	disruptive_inframe_deletion	Exon 9 of 10	NP_001944.1
TYMP	NM_001257989.1		c.1208_1213delCGCTGG	p.Ala403_Leu404del	disruptive_inframe_deletion	Exon 9 of 10	NP_001244918.1
TYMP	NM_001113755.3		c.1193_1198delCGCTGG	p.Ala398_Leu399del	disruptive_inframe_deletion	Exon 9 of 10	NP_001107227.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TYMP	ENST00000252029.8	TSL:1 MANE Select	c.1193_1198delCGCTGG	p.Ala398_Leu399del	disruptive_inframe_deletion	Exon 9 of 10	ENSP00000252029.3
TYMP	ENST00000395681.6	TSL:1	c.1208_1213delCGCTGG	p.Ala403_Leu404del	disruptive_inframe_deletion	Exon 9 of 10	ENSP00000379038.1
TYMP	ENST00000395678.7	TSL:1	c.1193_1198delCGCTGG	p.Ala398_Leu399del	disruptive_inframe_deletion	Exon 9 of 10	ENSP00000379036.3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000116

AC:

AN:

86072

AF XY:

0.0000205

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000319

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1337908

Hom.:

AF XY:

0.0000364

AC XY:

AN XY:

659574

show subpopulations

African (AFR)

AF:

0.0000372

AC:

AN:

26866

American (AMR)

AF:

0.00

AC:

AN:

29884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23354

East Asian (EAS)

AF:

0.00

AC:

AN:

30280

South Asian (SAS)

AF:

0.00

AC:

AN:

74328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4328

European-Non Finnish (NFE)

AF:

0.0000424

AC:

AN:

1060092

Other (OTH)

AF:

0.0000179

AC:

AN:

55732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74266

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000471

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions as Germline

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mitochondrial DNA depletion syndrome 1 (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=23/177

disease causing (ClinVar)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over