Variant rs344143 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.2983C>T(p.Leu995=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,572,822 control chromosomes in the GnomAD database, including 160,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14247 hom., cov: 31)

Exomes 𝑓: 0.45 ( 146067 hom. )

Consequence

SHROOM3
NM_020859.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0160

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-76741156-C-T is Benign according to our data. Variant chr4-76741156-C-T is described in ClinVar as [Benign]. Clinvar id is 403441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.016 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM3	NM_020859.4 linkuse as main transcript	c.2983C>T	p.Leu995=	synonymous_variant	5/11	ENST00000296043.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM3	ENST00000296043.7 linkuse as main transcript	c.2983C>T	p.Leu995=	synonymous_variant	5/11	1	NM_020859.4	P1	Q8TF72-1
SHROOM3-AS1	ENST00000666924.1 linkuse as main transcript	n.448+1652G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65369

AN:

151640

Hom.:

14219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.424

AC:

72525

AN:

170912

Hom.:

15564

AF XY:

0.424

AC XY:

39852

AN XY:

93980

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.437

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.451

AC:

640618

AN:

1421064

Hom.:

146067

Cov.:

AF XY:

0.449

AC XY:

316038

AN XY:

703388

show subpopulations

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.395

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.398

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.431

AC:

65449

AN:

151758

Hom.:

14247

Cov.:

AF XY:

0.427

AC XY:

31645

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.421

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.454

Hom.:

4985

Bravo

AF:

0.429

Asia WGS

AF:

0.328

AC:

1142

AN:

3478

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: Frequency -

SHROOM3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

DANN

Benign

0.67

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