Variant rs344142 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020859.4(SHROOM3):c.2922G>A(p.Ser974Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,544,448 control chromosomes in the GnomAD database, including 265,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22207 hom., cov: 31)

Exomes 𝑓: 0.58 ( 242881 hom. )

Consequence

SHROOM3
NM_020859.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.00

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 (HGNC:):

SHROOM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-76741095-G-A is Benign according to our data. Variant chr4-76741095-G-A is described in ClinVar as [Benign]. Clinvar id is 403440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 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.2922G>A	p.Ser974Ser	synonymous_variant	5/11	ENST00000296043.7	NP_065910.3	Q8TF72-1B3KY47
SHROOM3-AS1	NR_187404.1 linkuse as main transcript	n.1044+1713C>T		intron_variant
SHROOM3-AS1	NR_187405.1 linkuse as main transcript	n.500+1713C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7 linkuse as main transcript	c.2922G>A	p.Ser974Ser	synonymous_variant	5/11	1	NM_020859.4	ENSP00000296043.6		Q8TF72-1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80595

AN:

151750

Hom.:

22183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.540

GnomAD3 exomes

AF:

0.533

AC:

73212

AN:

137298

Hom.:

20360

AF XY:

0.530

AC XY:

39627

AN XY:

74726

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.515

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.585

AC:

814551

AN:

1392582

Hom.:

242881

Cov.:

AF XY:

0.582

AC XY:

399681

AN XY:

686732

show subpopulations

Gnomad4 AFR exome

AF:

0.413

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.646

Gnomad4 EAS exome

AF:

0.246

Gnomad4 SAS exome

AF:

0.446

Gnomad4 FIN exome

AF:

0.568

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.531

AC:

80672

AN:

151866

Hom.:

22207

Cov.:

AF XY:

0.525

AC XY:

38994

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.428

Gnomad4 FIN

AF:

0.578

Gnomad4 NFE

AF:

0.611

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.582

Hom.:

5302

Bravo

AF:

0.526

Asia WGS

AF:

0.350

AC:

1218

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

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: Frequency -

SHROOM3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 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

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

DANN

Benign

0.62

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