Variant 5-132824342-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001172700.2(SHROOM1):c.1319C>T(p.Pro440Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 1,608,256 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.418

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019893974).

BP6

Variant 5-132824342-G-A is Benign according to our data. Variant chr5-132824342-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2362042.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM1	NM_001172700.2 linkuse as main transcript	c.1319C>T	p.Pro440Leu	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.1319C>T	p.Pro440Leu	missense_variant	7/10	1	NM_001172700.2	P2	Q2M3G4-1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000573

AC:

139

AN:

242546

Hom.:

AF XY:

0.000550

AC XY:

AN XY:

130800

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.000849

Gnomad ASJ exome

AF:

0.000216

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000799

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.000554

AC:

807

AN:

1455898

Hom.:

Cov.:

AF XY:

0.000549

AC XY:

397

AN XY:

723778

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000811

Gnomad4 ASJ exome

AF:

0.000665

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000200

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000608

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000394

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000515

Hom.:

Bravo

AF:

0.000642

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000453

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.1319C>T (p.P440L) alteration is located in exon 7 (coding exon 4) of the SHROOM1 gene. This alteration results from a C to T substitution at nucleotide position 1319, causing the proline (P) at amino acid position 440 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

SHROOM1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 29, 2023

This variant is classified as likely 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

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

Cadd

Benign

7.4

Dann

Benign

0.85

DEOGEN2

Benign

0.050

T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.074

M_CAP

Benign

0.017

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

N;.;N;N

REVEL

Benign

0.0090

Sift

Uncertain

0.021

D;.;D;D

Sift4G

Benign

0.069

T;T;T;T

Polyphen

0.029

B;B;B;.

Vest4

0.16

MVP

0.40

MPC

0.014

ClinPred

0.017

GERP RS

2.3

Varity_R

0.047

gMVP

0.11

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