Variant 5-132822857-G-C 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.2498C>G(p.Pro833Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,613,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

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 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=0.089090735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM1	NM_001172700.2 linkuse as main transcript	c.2498C>G	p.Pro833Arg	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.2498C>G	p.Pro833Arg	missense_variant	10/10	1	NM_001172700.2	P2	Q2M3G4-1
SHROOM1	ENST00000319854.7 linkuse as main transcript	c.2483C>G	p.Pro828Arg	missense_variant	7/7	1		A2	Q2M3G4-2
SHROOM1	ENST00000617339.4 linkuse as main transcript	c.2498C>G	p.Pro833Arg	missense_variant	8/8	5		P2	Q2M3G4-1
SHROOM1	ENST00000378676.1 linkuse as main transcript	c.2291C>G	p.Pro764Arg	missense_variant	6/6	5		A2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

246152

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

133774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.000373

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000191

AC:

279

AN:

1460978

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

136

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000208

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000138

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

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

Mar 06, 2023

The c.2498C>G (p.P833R) alteration is located in exon 10 (coding exon 7) of the SHROOM1 gene. This alteration results from a C to G substitution at nucleotide position 2498, causing the proline (P) at amino acid position 833 to be replaced by an arginine (R). 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

0.082

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.64

Cadd

Benign

1.1

Dann

Benign

0.63

DEOGEN2

Benign

0.014

T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.15

M_CAP

Benign

0.026

MetaRNN

Benign

0.089

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.81

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

1.1

N;.;N;N

REVEL

Benign

0.15

Sift

Benign

0.081

T;.;T;T

Sift4G

Uncertain

0.055

T;T;T;T

Polyphen

0.97

D;D;D;.

Vest4

0.16

MVP

0.31

MPC

1.3

ClinPred

0.079

GERP RS

-4.8

Varity_R

0.033

gMVP

0.18

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