Variant X-9891058-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001649.4(SHROOM2):c.399A>G(p.Pro133Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.87 ( 29542 hom., 29245 hem., cov: 23)

Exomes 𝑓: 0.94 ( 321587 hom. 336402 hem. )

Failed GnomAD Quality Control

Consequence

SHROOM2
NM_001649.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.374

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-9891058-A-G is Benign according to our data. Variant chrX-9891058-A-G is described in ClinVar as [Benign]. Clinvar id is 3059401.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.374 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM2	NM_001649.4 linkuse as main transcript	c.399A>G	p.Pro133Pro	synonymous_variant	3/10	ENST00000380913.8	NP_001640.1	Q13796
SHROOM2	XM_005274500.5 linkuse as main transcript	c.399A>G	p.Pro133Pro	synonymous_variant	3/10		XP_005274557.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM2	ENST00000380913.8 linkuse as main transcript	c.399A>G	p.Pro133Pro	synonymous_variant	3/10	1	NM_001649.4	ENSP00000370299.3		Q13796

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

96295

AN:

111308

Hom.:

29549

Cov.:

AF XY:

0.872

AC XY:

29190

AN XY:

33482

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.987

Gnomad AMR

AF:

0.931

Gnomad ASJ

AF:

0.930

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.958

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.903

Gnomad NFE

AF:

0.939

Gnomad OTH

AF:

0.879

GnomAD3 exomes

AF:

0.929

AC:

149807

AN:

161308

Hom.:

47662

AF XY:

0.937

AC XY:

47540

AN XY:

50712

show subpopulations

Gnomad AFR exome

AF:

0.665

Gnomad AMR exome

AF:

0.957

Gnomad ASJ exome

AF:

0.920

Gnomad EAS exome

AF:

0.996

Gnomad SAS exome

AF:

0.960

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.940

Gnomad OTH exome

AF:

0.929

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.937

AC:

1022028

AN:

1091251

Hom.:

321587

Cov.:

AF XY:

0.939

AC XY:

336402

AN XY:

358305

show subpopulations

Gnomad4 AFR exome

AF:

0.662

Gnomad4 AMR exome

AF:

0.955

Gnomad4 ASJ exome

AF:

0.924

Gnomad4 EAS exome

AF:

0.993

Gnomad4 SAS exome

AF:

0.959

Gnomad4 FIN exome

AF:

0.940

Gnomad4 NFE exome

AF:

0.942

Gnomad4 OTH exome

AF:

0.923

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.865

AC:

96337

AN:

111359

Hom.:

29542

Cov.:

AF XY:

0.872

AC XY:

29245

AN XY:

33543

show subpopulations

Gnomad4 AFR

AF:

0.666

Gnomad4 AMR

AF:

0.932

Gnomad4 ASJ

AF:

0.930

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.957

Gnomad4 FIN

AF:

0.943

Gnomad4 NFE

AF:

0.939

Gnomad4 OTH

AF:

0.880

Alfa

AF:

0.905

Hom.:

11925

Bravo

AF:

0.856

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SHROOM2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 29, 2024

This variant is classified as 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

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.85

DANN

Benign

0.29

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