Variant rs879255268 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_198291.3(SRC):c.1579G>A(p.Glu527Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SRC
NM_198291.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

SRC (HGNC:11283): (SRC proto-oncogene, non-receptor tyrosine kinase) This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

SRC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

PP5

Variant 20-37403347-G-A is Pathogenic according to our data. Variant chr20-37403347-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225689.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRC	NM_198291.3 linkuse as main transcript	c.1579G>A	p.Glu527Lys	missense_variant	14/14	ENST00000373578.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRC	ENST00000373578.7 linkuse as main transcript	c.1579G>A	p.Glu527Lys	missense_variant	14/14	5	NM_198291.3	P1	P12931-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Thrombocytopenia 6

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 12, 2021	- -

Primary myelofibrosis;C0029456:Osteoporosis;C0040034:Thrombocytopenia

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

D;D;D;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

.;D;.;D

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.78

D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.033

D;D;D;D

Polyphen

0.99

D;D;D;.

Vest4

0.86

MutPred

0.39

Gain of ubiquitination at E527 (P = 0.009);Gain of ubiquitination at E527 (P = 0.009);Gain of ubiquitination at E527 (P = 0.009);.;

MVP

0.54

MPC

2.8

ClinPred

1.0

GERP RS

4.7

Varity_R

0.93

gMVP

0.83

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

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