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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020717.5(SHROOM4):c.3411_3413dupGGA(p.Glu1138dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,091,571 control chromosomes in the GnomAD database, including 29,069 homozygotes. There are 71,921 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 3319 hom., 6730 hem., cov: 14)

Exomes 𝑓: 0.28 ( 25750 hom. 65191 hem. )

Consequence

SHROOM4
NM_020717.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.350

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:

SHROOM4 (HGNC:):

SHROOM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-50607728-T-TTCC is Benign according to our data. Variant chrX-50607728-T-TTCC is described in ClinVar as [Benign]. Clinvar id is 95971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5 linkuse as main transcript	c.3411_3413dupGGA	p.Glu1138dup	disruptive_inframe_insertion	6/9	ENST00000376020.9	NP_065768.2	Q9ULL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SHROOM4	ENST00000376020.9 linkuse as main transcript	c.3411_3413dupGGA	p.Glu1138dup	disruptive_inframe_insertion	6/9	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 linkuse as main transcript	c.3411_3413dupGGA	p.Glu1138dup	disruptive_inframe_insertion	6/10	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 linkuse as main transcript	c.3063_3065dupGGA	p.Glu1022dup	disruptive_inframe_insertion	5/8	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

28804

AN:

105509

Hom.:

3329

Cov.:

AF XY:

0.235

AC XY:

6729

AN XY:

28603

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.353

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.212

AC:

26912

AN:

127114

Hom.:

1812

AF XY:

0.103

AC XY:

3362

AN XY:

32658

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.283

AC:

278624

AN:

986025

Hom.:

25750

Cov.:

AF XY:

0.229

AC XY:

65191

AN XY:

284763

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.273

AC:

28779

AN:

105546

Hom.:

3319

Cov.:

AF XY:

0.235

AC XY:

6730

AN XY:

28652

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.290

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 29, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jun 19, 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. -
Benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 11, 2013	- -

X-linked intellectual disability, Stocco dos Santos type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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