Variant 18-751739-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005433.4(YES1):c.337A>C(p.Lys113Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,601,440 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 47 hom. )

Consequence

YES1
NM_005433.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

YES1 (HGNC:12841): (YES proto-oncogene 1, Src family tyrosine kinase) This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]

YES1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009892702).

BP6

Variant 18-751739-T-G is Benign according to our data. Variant chr18-751739-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2648515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 875 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YES1	NM_005433.4 linkuse as main transcript	c.337A>C	p.Lys113Gln	missense_variant	3/12	ENST00000314574.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
YES1	ENST00000314574.5 linkuse as main transcript	c.337A>C	p.Lys113Gln	missense_variant	3/12	1	NM_005433.4	P1
YES1	ENST00000584307.5 linkuse as main transcript	c.337A>C	p.Lys113Gln	missense_variant	3/12	1		P1
YES1	ENST00000577961.5 linkuse as main transcript	c.352A>C	p.Lys118Gln	missense_variant	3/12	5
YES1	ENST00000577611.1 linkuse as main transcript	n.553A>C		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

875

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00791

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00550

AC:

1381

AN:

250892

Hom.:

AF XY:

0.00544

AC XY:

738

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.00694

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00641

AC:

9282

AN:

1449158

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

4540

AN XY:

721710

show subpopulations

Gnomad4 AFR exome

AF:

0.000723

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.000998

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.00685

Gnomad4 OTH exome

AF:

0.00615

GnomAD4 genome

AF:

0.00575

AC:

875

AN:

152282

Hom.:

Cov.:

AF XY:

0.00628

AC XY:

468

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0198

Gnomad4 NFE

AF:

0.00791

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00663

Hom.:

Bravo

AF:

0.00429

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00544

AC:

661

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00622

EpiControl

AF:

0.00587

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

YES1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;.;D

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0010

.;B;B

Vest4

0.52

MVP

0.49

MPC

0.35

ClinPred

0.025

GERP RS

5.8

Varity_R

0.50

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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