Variant chr1-154966186-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001130040.2(SHC1):c.1228A>G(p.Met410Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 1,614,014 control chromosomes in the GnomAD database, including 1,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.062 ( 477 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1283 hom. )

Consequence

SHC1
NM_001130040.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

Variant links:

Genes affected

SHC1 (HGNC:10840): (SHC adaptor protein 1) This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

SHC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013918281).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC1	NM_001130040.2 linkuse as main transcript	c.1228A>G	p.Met410Val	missense_variant	9/12	ENST00000448116.7	NP_001123512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC1	ENST00000448116.7 linkuse as main transcript	c.1228A>G	p.Met410Val	missense_variant	9/12	1	NM_001130040.2	ENSP00000401303	A1	P29353-6

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

9341

AN:

152084

Hom.:

468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0521

GnomAD3 exomes

AF:

0.0415

AC:

10421

AN:

251316

Hom.:

342

AF XY:

0.0404

AC XY:

5493

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0244

Gnomad ASJ exome

AF:

0.0367

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.0564

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.0389

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0361

AC:

52821

AN:

1461812

Hom.:

1283

Cov.:

AF XY:

0.0364

AC XY:

26472

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.0260

Gnomad4 ASJ exome

AF:

0.0372

Gnomad4 EAS exome

AF:

0.00181

Gnomad4 SAS exome

AF:

0.0563

Gnomad4 FIN exome

AF:

0.0225

Gnomad4 NFE exome

AF:

0.0331

Gnomad4 OTH exome

AF:

0.0397

GnomAD4 genome

AF:

0.0617

AC:

9390

AN:

152202

Hom.:

477

Cov.:

AF XY:

0.0599

AC XY:

4455

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.0294

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.00520

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.0207

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0325

Hom.:

Bravo

AF:

0.0640

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0317

AC:

122

ESP6500AA

AF:

0.135

AC:

597

ESP6500EA

AF:

0.0350

AC:

301

ExAC

AF:

0.0454

AC:

5512

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

EpiCase

AF:

0.0376

EpiControl

AF:

0.0370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.32

T;.;T;.;.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.37

T;T;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

N;N;.;.;.;.

MutationTaster

Benign

0.56

P;P;P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.020

N;N;.;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.62

T;T;.;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T;T

Polyphen

0.0

B;B;.;.;.;.

Vest4

0.13

MPC

0.36

ClinPred

0.0012

GERP RS

1.8

Varity_R

0.080

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over