Variant 5-132824298-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001172700.2(SHROOM1):c.1363C>A(p.Gln455Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,613,662 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 2 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

SHROOM1 (HGNC:24084): (shroom family member 1) SHROOM family members play diverse roles in the development of the nervous system and other tissues (Hagens et al., 2006 [PubMed 16615870]).[supplied by OMIM, Mar 2008]

SHROOM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031650454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM1	NM_001172700.2 linkuse as main transcript	c.1363C>A	p.Gln455Lys	missense_variant	7/10	ENST00000378679.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM1	ENST00000378679.8 linkuse as main transcript	c.1363C>A	p.Gln455Lys	missense_variant	7/10	1	NM_001172700.2	P2	Q2M3G4-1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000473

AC:

118

AN:

249310

Hom.:

AF XY:

0.000482

AC XY:

AN XY:

134776

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000898

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000687

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.000584

AC:

853

AN:

1461316

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

416

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000711

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000479

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000642

Hom.:

Bravo

AF:

0.000499

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000949

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1363C>A (p.Q455K) alteration is located in exon 7 (coding exon 4) of the SHROOM1 gene. This alteration results from a C to A substitution at nucleotide position 1363, causing the glutamine (Q) at amino acid position 455 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.39

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;.;T

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.25

M_CAP

Benign

0.011

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.64

N;.;N;N

REVEL

Benign

0.048

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Uncertain

0.038

D;D;D;D

Polyphen

0.89

P;P;P;.

Vest4

0.33

MVP

0.43

MPC

0.017

ClinPred

0.077

GERP RS

4.0

Varity_R

0.26

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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