Variant 4-76738792-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_020859.4(SHROOM3):c.619C>T(p.His207Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,614,234 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.48

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056450963).

BP6

Variant 4-76738792-C-T is Benign according to our data. Variant chr4-76738792-C-T is described in ClinVar as [Benign]. Clinvar id is 3050398.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-76738792-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4 linkuse as main transcript	c.619C>T	p.His207Tyr	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.619C>T	p.His207Tyr	missense_variant	5/11	1	NM_020859.4	ENSP00000296043	P1	Q8TF72-1
SHROOM3-AS1	ENST00000666924.1 linkuse as main transcript	n.448+4016G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

354

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00743

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00301

AC:

756

AN:

251368

Hom.:

AF XY:

0.00293

AC XY:

398

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00850

Gnomad NFE exome

AF:

0.00473

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00298

AC:

4351

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2119

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00745

Gnomad4 NFE exome

AF:

0.00338

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00232

AC:

354

AN:

152354

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00743

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00161

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00359

AC:

436

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SHROOM3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

0.97

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.9

D;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.016

D;.

Polyphen

1.0

D;.

Vest4

0.41

MVP

0.31

MPC

0.98

ClinPred

0.046

GERP RS

6.1

Varity_R

0.45

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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