Variant 5-132822930-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001172700.2(SHROOM1):c.2425C>T(p.Arg809Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,532 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.132

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26049626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM1	NM_001172700.2 linkuse as main transcript	c.2425C>T	p.Arg809Cys	missense_variant	10/10	ENST00000378679.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM1	ENST00000378679.8 linkuse as main transcript	c.2425C>T	p.Arg809Cys	missense_variant	10/10	1	NM_001172700.2	P2	Q2M3G4-1
SHROOM1	ENST00000319854.7 linkuse as main transcript	c.2410C>T	p.Arg804Cys	missense_variant	7/7	1		A2	Q2M3G4-2
SHROOM1	ENST00000617339.4 linkuse as main transcript	c.2425C>T	p.Arg809Cys	missense_variant	8/8	5		P2	Q2M3G4-1
SHROOM1	ENST00000378676.1 linkuse as main transcript	c.2218C>T	p.Arg740Cys	missense_variant	6/6	5		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245320

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460532

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 28, 2024

The c.2425C>T (p.R809C) alteration is located in exon 10 (coding exon 7) of the SHROOM1 gene. This alteration results from a C to T substitution at nucleotide position 2425, causing the arginine (R) at amino acid position 809 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.074

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.4

D;.;D;D

REVEL

Benign

0.061

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.50

P;P;B;.

Vest4

0.21

MutPred

0.75

Loss of disorder (P = 0.0347);Loss of disorder (P = 0.0347);.;.;

MVP

0.53

MPC

1.9

ClinPred

0.97

GERP RS

1.2

Varity_R

0.32

gMVP

0.28

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