Variant X-50607728-TTCCTCC-TTCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_020717.5(SHROOM4):c.3411_3413del(p.Glu1151del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,111,158 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 64 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., 10 hem., cov: 14)

Exomes 𝑓: 0.00029 ( 0 hom. 54 hem. )

Consequence

SHROOM4
NM_020717.5 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.943

Variant links:

Genes affected

SHROOM4 (HGNC:29215): (shroom family member 4) This gene encodes a member of the APX/Shroom family, which contain an N-terminal PDZ domain and a C-terminal ASD2 motif. The encoded protein may play a role in cytoskeletal architecture. Mutations in this gene have been linked to the X-linked Stocco dos Santos syndrome characterized by cognitive disabilities. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2017]

SHROOM4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-50607728-TTCC-T is Benign according to our data. Variant chrX-50607728-TTCC-T is described in ClinVar as [Benign]. Clinvar id is 590248.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5 linkuse as main transcript	c.3411_3413del	p.Glu1151del	inframe_deletion	6/9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9 linkuse as main transcript	c.3411_3413del	p.Glu1151del	inframe_deletion	6/9	2	NM_020717.5	ENSP00000365188	P1	Q9ULL8-1
SHROOM4	ENST00000289292.11 linkuse as main transcript	c.3411_3413del	p.Glu1151del	inframe_deletion	6/10	1		ENSP00000289292	P1	Q9ULL8-1
SHROOM4	ENST00000460112.3 linkuse as main transcript	c.3063_3065del	p.Glu1035del	inframe_deletion	5/8	5		ENSP00000421450		Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.000426

AC:

AN:

105667

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

28681

show subpopulations

Gnomad AFR

AF:

0.000388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000605

Gnomad ASJ

AF:

0.00234

Gnomad EAS

AF:

0.00178

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00431

Gnomad NFE

AF:

0.000272

Gnomad OTH

AF:

0.000717

GnomAD3 exomes

AF:

0.000598

AC:

AN:

127114

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

32658

show subpopulations

Gnomad AFR exome

AF:

0.000335

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00257

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.000265

Gnomad FIN exome

AF:

0.000166

Gnomad NFE exome

AF:

0.000539

Gnomad OTH exome

AF:

0.000926

GnomAD4 exome

AF:

0.000285

AC:

287

AN:

1005455

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

301399

show subpopulations

Gnomad4 AFR exome

AF:

0.000413

Gnomad4 AMR exome

AF:

0.000397

Gnomad4 ASJ exome

AF:

0.00221

Gnomad4 EAS exome

AF:

0.000414

Gnomad4 SAS exome

AF:

0.000414

Gnomad4 FIN exome

AF:

0.000156

Gnomad4 NFE exome

AF:

0.000228

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000426

AC:

AN:

105703

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

AN XY:

28729

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.000604

Gnomad4 ASJ

AF:

0.00234

Gnomad4 EAS

AF:

0.00179

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000272

Gnomad4 OTH

AF:

0.000708

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

SHROOM4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as likely 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

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