Variant 4-76555619-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020859.4(SHROOM3):c.179G>T(p.Gly60Val) variant causes a missense change. The variant allele was found at a frequency of 0.00208 in 1,613,742 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0021 ( 4 hom. )

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.34

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045105994).

BP6

Variant 4-76555619-G-T is Benign according to our data. Variant chr4-76555619-G-T is described in ClinVar as [Benign]. Clinvar id is 1686322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4 linkuse as main transcript	c.179G>T	p.Gly60Val	missense_variant	2/11	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.179G>T	p.Gly60Val	missense_variant	2/11	1	NM_020859.4	ENSP00000296043	P1	Q8TF72-1
SHROOM3	ENST00000466541.1 linkuse as main transcript	n.86G>T		non_coding_transcript_exon_variant	2/3	3
SHROOM3	ENST00000469923.5 linkuse as main transcript	n.6G>T		non_coding_transcript_exon_variant	1/5	3
SHROOM3	ENST00000497440.5 linkuse as main transcript	n.120G>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00203

AC:

509

AN:

251326

Hom.:

AF XY:

0.00208

AC XY:

283

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00285

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00214

AC:

3123

AN:

1461426

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

1588

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00329

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

152316

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00191

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00202

AC:

245

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00308

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

Mendelics

May 04, 2022

- -

SHROOM3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2022

This variant is classified as likely 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.071

MetaRNN

Benign

0.045

MetaSVM

Uncertain

0.14

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.69

MVP

0.52

MPC

1.1

ClinPred

0.11

GERP RS

5.0

Varity_R

0.85

gMVP

0.71

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