rs11479

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000252029.8(TYMP):c.1412C>T(p.Ser471Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 1,610,390 control chromosomes in the GnomAD database, including 9,556 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S471S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.090 ( 778 hom., cov: 35)

Exomes 𝑓: 0.10 ( 8778 hom. )

Consequence

TYMP
ENST00000252029.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 1.14

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021177828).

BP6

Variant 22-50525807-G-A is Benign according to our data. Variant chr22-50525807-G-A is described in ClinVar as [Benign]. Clinvar id is 130693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50525807-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYMP	NM_001953.5 linkuse as main transcript	c.1412C>T	p.Ser471Leu	missense_variant	10/10	ENST00000252029.8	NP_001944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYMP	ENST00000252029.8 linkuse as main transcript	c.1412C>T	p.Ser471Leu	missense_variant	10/10	1	NM_001953.5	ENSP00000252029	P2	P19971-1

Frequencies

GnomAD3 genomes

AF:

0.0899

AC:

13689

AN:

152208

Hom.:

778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0697

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.0908

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0866

Gnomad OTH

AF:

0.0969

GnomAD3 exomes

AF:

0.128

AC:

29384

AN:

230034

Hom.:

2415

AF XY:

0.125

AC XY:

15971

AN XY:

127710

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.0688

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.0933

Gnomad NFE exome

AF:

0.0885

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.100

AC:

146515

AN:

1458068

Hom.:

8778

Cov.:

AF XY:

0.102

AC XY:

74188

AN XY:

725332

show subpopulations

Gnomad4 AFR exome

AF:

0.0482

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.0685

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.0947

Gnomad4 NFE exome

AF:

0.0885

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0899

AC:

13695

AN:

152322

Hom.:

778

Cov.:

AF XY:

0.0928

AC XY:

6912

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0506

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.0697

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.0908

Gnomad4 NFE

AF:

0.0866

Gnomad4 OTH

AF:

0.0969

Alfa

AF:

0.0876

Hom.:

613

Bravo

AF:

0.0900

TwinsUK

AF:

0.0823

AC:

305

ALSPAC

AF:

0.0924

AC:

356

ESP6500AA

AF:

0.0440

AC:

183

ESP6500EA

AF:

0.0807

AC:

663

ExAC

AF:

0.120

AC:

14146

Asia WGS

AF:

0.229

AC:

793

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2011	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Mitochondrial DNA depletion syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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. -
Benign, no assertion criteria provided	literature only	GeneReviews	Jan 14, 2016	- -

Spinal muscular atrophy

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Fatal Infantile Cardioencephalomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;.;T;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.67

.;T;.;T;T

MetaRNN

Benign

0.0021

T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.7

L;.;L;L;.

MutationTaster

Benign

2.1e-11

P;P;P;P;P;P

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.61

N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.40

T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.99

D;.;D;D;.

Vest4

0.28

MPC

0.92

ClinPred

0.033

GERP RS

2.2

Varity_R

0.14

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over