Variant 4-76730904-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_020859.4(SHROOM3):c.556G>C(p.Gly186Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,614,090 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 151 hom. )

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.82

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029561818).

BP6

Variant 4-76730904-G-C is Benign according to our data. Variant chr4-76730904-G-C is described in ClinVar as [Benign]. Clinvar id is 3038663.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-76730904-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00154 (234/152222) while in subpopulation SAS AF= 0.0473 (228/4816). AF 95% confidence interval is 0.0423. There are 9 homozygotes in gnomad4. There are 176 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4 linkuse as main transcript	c.556G>C	p.Gly186Arg	missense_variant	4/11	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.556G>C	p.Gly186Arg	missense_variant	4/11	1	NM_020859.4	ENSP00000296043	P1	Q8TF72-1
SHROOM3-AS1	ENST00000666924.1 linkuse as main transcript	n.448+11904C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

236

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0477

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00632

AC:

1589

AN:

251478

Hom.:

AF XY:

0.00867

AC XY:

1179

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00313

AC:

4578

AN:

1461868

Hom.:

151

Cov.:

AF XY:

0.00465

AC XY:

3382

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0501

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

152222

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0473

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000305

Hom.:

Bravo

AF:

0.000382

ExAC

AF:

0.00727

AC:

883

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

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

May 22, 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.3

D;.;.

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.049

D;.;.

Polyphen

0.99

D;.;.

Vest4

0.80

MVP

0.57

MPC

1.1

ClinPred

0.11

GERP RS

4.9

Varity_R

0.38

gMVP

0.38

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