Variant 5-132823032-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172700.2(SHROOM1):c.2323G>A(p.Glu775Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,599,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028406113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM1	NM_001172700.2 linkuse as main transcript	c.2323G>A	p.Glu775Lys	missense_variant	10/10	ENST00000378679.8	NP_001166171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM1	ENST00000378679.8 linkuse as main transcript	c.2323G>A	p.Glu775Lys	missense_variant	10/10	1	NM_001172700.2	ENSP00000367950	P2	Q2M3G4-1
SHROOM1	ENST00000319854.7 linkuse as main transcript	c.2308G>A	p.Glu770Lys	missense_variant	7/7	1		ENSP00000324245	A2	Q2M3G4-2
SHROOM1	ENST00000617339.4 linkuse as main transcript	c.2323G>A	p.Glu775Lys	missense_variant	8/8	5		ENSP00000478436	P2	Q2M3G4-1
SHROOM1	ENST00000378676.1 linkuse as main transcript	c.2116G>A	p.Glu706Lys	missense_variant	6/6	5		ENSP00000367947	A2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

225978

Hom.:

AF XY:

0.0000802

AC XY:

AN XY:

124760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000881

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00135

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:

0.0000414

AC:

AN:

1447610

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

720590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000998

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 20, 2024

The c.2323G>A (p.E775K) alteration is located in exon 10 (coding exon 7) of the SHROOM1 gene. This alteration results from a G to A substitution at nucleotide position 2323, causing the glutamic acid (E) at amino acid position 775 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

0.21

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.83

.;T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.028

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

D;.;D;D

REVEL

Benign

0.11

Sift

Benign

0.13

T;.;T;T

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

0.69

P;P;P;.

Vest4

0.24

MutPred

0.57

Gain of MoRF binding (P = 0.0093);Gain of MoRF binding (P = 0.0093);.;.;

MVP

0.39

MPC

1.7

ClinPred

0.17

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.098

gMVP

0.13

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