Variant 1-154486662-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010846.3(SHE):c.1046G>A(p.Arg349Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000106 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SHE
NM_001010846.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

Variant links:

Genes affected

SHE (HGNC:27004): (Src homology 2 domain containing E) Predicted to enable phosphotyrosine residue binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SHE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24511385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SHE	NM_001010846.3 linkuse as main transcript	c.1046G>A	p.Arg349Gln	missense_variant	4/6	ENST00000304760.3
SHE	XM_011509163.4 linkuse as main transcript	c.1046G>A	p.Arg349Gln	missense_variant	4/7
SHE	XM_005244891.6 linkuse as main transcript	c.1046G>A	p.Arg349Gln	missense_variant	4/6
SHE	NR_135169.2 linkuse as main transcript	n.1427G>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHE	ENST00000304760.3 linkuse as main transcript	c.1046G>A	p.Arg349Gln	missense_variant	4/6	1	NM_001010846.3	P1
SHE	ENST00000555188.5 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251376

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000106

AC:

155

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000105

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000983

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.1046G>A (p.R349Q) alteration is located in exon 4 (coding exon 4) of the SHE gene. This alteration results from a G to A substitution at nucleotide position 1046, causing the arginine (R) at amino acid position 349 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.34

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.060

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.019

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.7

REVEL

Benign

0.17

Sift

Uncertain

0.017

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.28

MVP

0.48

MPC

1.2

ClinPred

0.38

GERP RS

5.6

Varity_R

0.21

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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