Variant X-9894539-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_ModerateBP4BS2_Supporting

The NM_001649.4(SHROOM2):c.631G>A(p.Gly211Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,209,486 control chromosomes in the GnomAD database, including 12 homozygotes. There are 1,276 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., 87 hem., cov: 24)

Exomes 𝑓: 0.0034 ( 11 hom. 1189 hem. )

Consequence

SHROOM2
NM_001649.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.45

Variant links:

Genes affected

SHROOM2 (HGNC:630): (shroom family member 2) This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

SHROOM2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant X-9894539-G-A is Pathogenic according to our data. Variant chrX-9894539-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1174005.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.006932944). . Strength limited to SUPPORTING due to the PP5.

BS2

High Hemizygotes in GnomAd4 at 87 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM2	NM_001649.4 link	c.631G>A	p.Gly211Ser	missense_variant	4/10	ENST00000380913.8	NP_001640.1	Q13796
SHROOM2	XM_005274500.5 link	c.631G>A	p.Gly211Ser	missense_variant	4/10		XP_005274557.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM2	ENST00000380913.8 link	c.631G>A	p.Gly211Ser	missense_variant	4/10	1	NM_001649.4	ENSP00000370299.3		Q13796

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

259

AN:

111291

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

AN XY:

33479

show subpopulations

Gnomad AFR

AF:

0.000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00338

GnomAD3 exomes

AF:

0.00346

AC:

632

AN:

182798

Hom.:

AF XY:

0.00343

AC XY:

231

AN XY:

67380

show subpopulations

Gnomad AFR exome

AF:

0.000457

Gnomad AMR exome

AF:

0.000766

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.00405

Gnomad OTH exome

AF:

0.00553

GnomAD4 exome

AF:

0.00336

AC:

3694

AN:

1098146

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

1189

AN XY:

363514

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.000710

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.00336

Gnomad4 OTH exome

AF:

0.00312

GnomAD4 genome

AF:

0.00231

AC:

257

AN:

111340

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

AN XY:

33538

show subpopulations

Gnomad4 AFR

AF:

0.000261

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00180

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00346

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00312

AC:

ExAC

AF:

0.00355

AC:

431

EpiCase

AF:

0.00245

EpiControl

AF:

0.00296

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Meniere disease

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

case-control

Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO)

Jun 21, 2021

Digenic inheritance along with NM_000260.4:c.3G>A(MYO7A) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.38

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.9

REVEL

Benign

0.22

Sift

Benign

0.42

Sift4G

Benign

0.95

Polyphen

0.97

Vest4

0.061

MVP

0.68

MPC

0.42

ClinPred

0.022

GERP RS

3.3

Varity_R

0.12

gMVP

0.27

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