Variant X-9891070-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001649.4(SHROOM2):c.411C>T(p.Thr137Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,203,896 control chromosomes in the GnomAD database, including 190 homozygotes. There are 2,863 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., 408 hem., cov: 25)

Exomes 𝑓: 0.0060 ( 169 hom. 2455 hem. )

Consequence

SHROOM2
NM_001649.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.987

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-9891070-C-T is Benign according to our data. Variant chrX-9891070-C-T is described in ClinVar as [Benign]. Clinvar id is 3055522.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.987 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM2	NM_001649.4 linkuse as main transcript	c.411C>T	p.Thr137Thr	synonymous_variant	3/10	ENST00000380913.8	NP_001640.1	Q13796
SHROOM2	XM_005274500.5 linkuse as main transcript	c.411C>T	p.Thr137Thr	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.411C>T	p.Thr137Thr	synonymous_variant	3/10	1	NM_001649.4	ENSP00000370299.3		Q13796

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1256

AN:

112552

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

403

AN XY:

34680

show subpopulations

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00869

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0940

Gnomad SAS

AF:

0.0471

Gnomad FIN

AF:

0.00129

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.000657

Gnomad OTH

AF:

0.00855

GnomAD3 exomes

AF:

0.0150

AC:

2449

AN:

163359

Hom.:

AF XY:

0.0142

AC XY:

742

AN XY:

52111

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.0398

Gnomad FIN exome

AF:

0.00163

Gnomad NFE exome

AF:

0.000516

Gnomad OTH exome

AF:

0.0115

GnomAD4 exome

AF:

0.00599

AC:

6534

AN:

1091292

Hom.:

169

Cov.:

AF XY:

0.00686

AC XY:

2455

AN XY:

357958

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0931

Gnomad4 SAS exome

AF:

0.0386

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.000291

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0112

AC:

1260

AN:

112604

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

408

AN XY:

34742

show subpopulations

Gnomad4 AFR

AF:

0.0209

Gnomad4 AMR

AF:

0.00868

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0943

Gnomad4 SAS

AF:

0.0462

Gnomad4 FIN

AF:

0.00129

Gnomad4 NFE

AF:

0.000675

Gnomad4 OTH

AF:

0.00909

Alfa

AF:

0.00447

Hom.:

Bravo

AF:

0.0125

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

Mar 20, 2019

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

-0.81

CADD

Benign

1.0

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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