Variant 4-76739228-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020859.4(SHROOM3):c.1055G>A(p.Arg352Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,613,972 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00096 ( 1 hom. )

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.28

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01722306).

BP6

Variant 4-76739228-G-A is Benign according to our data. Variant chr4-76739228-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 732366.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4 linkuse as main transcript	c.1055G>A	p.Arg352Gln	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.1055G>A	p.Arg352Gln	missense_variant	5/11	1	NM_020859.4	ENSP00000296043	P1	Q8TF72-1
SHROOM3-AS1	ENST00000666924.1 linkuse as main transcript	n.448+3580C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000853

AC:

214

AN:

250826

Hom.:

AF XY:

0.000951

AC XY:

129

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000959

AC:

1402

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

665

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.00107

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152160

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000927

Hom.:

Bravo

AF:

0.000740

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00114

AC:

138

EpiCase

AF:

0.000654

EpiControl

AF:

0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.094

T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.017

T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.76

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;.

Sift4G

Benign

0.081

T;.

Polyphen

1.0

D;.

Vest4

0.13

MVP

0.62

MPC

0.99

ClinPred

0.036

GERP RS

5.7

Varity_R

0.13

gMVP

0.15

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