chr4-76739146-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020859.4(SHROOM3):c.973T>G(p.Ser325Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,614,028 control chromosomes in the GnomAD database, including 5,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 371 hom., cov: 33)

Exomes 𝑓: 0.080 ( 5211 hom. )

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.68

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018060207).

BP6

Variant 4-76739146-T-G is Benign according to our data. Variant chr4-76739146-T-G is described in ClinVar as Benign. ClinVar VariationId is 403438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4 link	c.973T>G	p.Ser325Ala	missense_variant	Exon 5 of 11	ENST00000296043.7	NP_065910.3	Q8TF72-1B3KY47
SHROOM3-AS1	NR_187404.1 link	n.1044+3662A>C		intron_variant	Intron 3 of 3
SHROOM3-AS1	NR_187405.1 link	n.500+3662A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7 link	c.973T>G	p.Ser325Ala	missense_variant	Exon 5 of 11	1	NM_020859.4	ENSP00000296043.6		Q8TF72-1

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8877

AN:

152120

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0413

Gnomad FIN

AF:

0.0638

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0845

Gnomad OTH

AF:

0.0789

GnomAD2 exomes

AF:

0.0643

AC:

16146

AN:

251086

AF XY:

0.0658

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.0641

Gnomad NFE exome

AF:

0.0887

Gnomad OTH exome

AF:

0.0800

GnomAD4 exome

AF:

0.0803

AC:

117433

AN:

1461790

Hom.:

5211

Cov.:

AF XY:

0.0795

AC XY:

57790

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.0151

AC:

505

AN:

33478

American (AMR)

AF:

0.0486

AC:

2172

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

2982

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39698

South Asian (SAS)

AF:

0.0425

AC:

3662

AN:

86256

European-Finnish (FIN)

AF:

0.0624

AC:

3333

AN:

53394

Middle Eastern (MID)

AF:

0.118

AC:

680

AN:

5768

European-Non Finnish (NFE)

AF:

0.0893

AC:

99337

AN:

1111946

Other (OTH)

AF:

0.0788

AC:

4756

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6833

13665

20498

27330

34163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3584

7168

10752

14336

17920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0582

AC:

8866

AN:

152238

Hom.:

371

Cov.:

AF XY:

0.0566

AC XY:

4213

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0152

AC:

631

AN:

41558

American (AMR)

AF:

0.0622

AC:

952

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

402

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0407

AC:

196

AN:

4818

European-Finnish (FIN)

AF:

0.0638

AC:

677

AN:

10608

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0845

AC:

5748

AN:

67988

Other (OTH)

AF:

0.0777

AC:

164

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

433

866

1300

1733

2166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0766

Hom.:

1151

Bravo

AF:

0.0587

TwinsUK

AF:

0.0866

AC:

321

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0929

AC:

799

ExAC

AF:

0.0629

AC:

7640

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0985

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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: MAF -

SHROOM3-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.

PhyloP100

2.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.084

Sift

Benign

0.048

D;.

Sift4G

Benign

0.18

T;.

Polyphen

0.95

P;.

Vest4

0.090

MPC

0.35

ClinPred

0.023

GERP RS

3.8

Varity_R

0.062

gMVP

0.27

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over