4-76739146-T-G

Position:

chr4-76739146-T-G

Variant summary

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

The NM_020859.4(SHROOM3):c.973T>G(p.Ser325Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,614,028 control chromosomes in the GnomAD database, including 5,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 371 hom., cov: 33)

Exomes 𝑓: 0.080 ( 5211 hom. )

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

SHROOM3 (HGNC:30422): (shroom family member 3) This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

SHROOM3 links:

SHROOM3-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

SHROOM3-AS1 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=0.0018060207).

BP6

Variant 4-76739146-T-G is Benign according to our data. Variant chr4-76739146-T-G is described in ClinVar as [Benign]. Clinvar id is 403438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-76739146-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4 linkuse as main transcript	c.973T>G	p.Ser325Ala	missense_variant	5/11	ENST00000296043.7	NP_065910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7 linkuse as main transcript	c.973T>G	p.Ser325Ala	missense_variant	5/11	1	NM_020859.4	ENSP00000296043	P1	Q8TF72-1
SHROOM3-AS1	ENST00000666924.1 linkuse as main transcript	n.448+3662A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8877

AN:

152120

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0413

Gnomad FIN

AF:

0.0638

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0845

Gnomad OTH

AF:

0.0789

GnomAD3 exomes

AF:

0.0643

AC:

16146

AN:

251086

Hom.:

677

AF XY:

0.0658

AC XY:

8928

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.0407

Gnomad FIN exome

AF:

0.0641

Gnomad NFE exome

AF:

0.0887

Gnomad OTH exome

AF:

0.0800

GnomAD4 exome

AF:

0.0803

AC:

117433

AN:

1461790

Hom.:

5211

Cov.:

AF XY:

0.0795

AC XY:

57790

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.0486

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0425

Gnomad4 FIN exome

AF:

0.0624

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0788

GnomAD4 genome

AF:

0.0582

AC:

8866

AN:

152238

Hom.:

371

Cov.:

AF XY:

0.0566

AC XY:

4213

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.0622

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0407

Gnomad4 FIN

AF:

0.0638

Gnomad4 NFE

AF:

0.0845

Gnomad4 OTH

AF:

0.0777

Alfa

AF:

0.0816

Hom.:

832

Bravo

AF:

0.0587

TwinsUK

AF:

0.0866

AC:

321

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0929

AC:

799

ExAC

AF:

0.0629

AC:

7640

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0985

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

SHROOM3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

0.77

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.084

Sift

Benign

0.048

D;.

Sift4G

Benign

0.18

T;.

Polyphen

0.95

P;.

Vest4

0.090

MPC

0.35

ClinPred

0.023

GERP RS

3.8

Varity_R

0.062

gMVP

0.27

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