Variant rs201922875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_020717.5(SHROOM4):c.3372_3383dupACAGCAGCAGCA(p.Gln1125_Gln1128dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 6130 hom., 9764 hem., cov: 0)

Exomes 𝑓: 0.35 ( 46031 hom. 125882 hem. )

Failed GnomAD Quality Control

Consequence

SHROOM4
NM_020717.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.676

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP6

Variant X-50607758-C-CTGCTGCTGCTGT is Benign according to our data. Variant chrX-50607758-C-CTGCTGCTGCTGT is described in ClinVar as [Benign]. Clinvar id is 95970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5 linkuse as main transcript	c.3372_3383dupACAGCAGCAGCA	p.Gln1125_Gln1128dup	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.3372_3383dupACAGCAGCAGCA	p.Gln1125_Gln1128dup	disruptive_inframe_insertion	6/9	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 linkuse as main transcript	c.3372_3383dupACAGCAGCAGCA	p.Gln1125_Gln1128dup	disruptive_inframe_insertion	6/10	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 linkuse as main transcript	c.3024_3035dupACAGCAGCAGCA	p.Gln1009_Gln1012dup	disruptive_inframe_insertion	5/8	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

39596

AN:

107497

Hom.:

6135

Cov.:

AF XY:

0.322

AC XY:

9739

AN XY:

30221

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.412

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.308

AC:

50914

AN:

165426

Hom.:

6199

AF XY:

0.288

AC XY:

15922

AN XY:

55350

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.244

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.339

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.351

AC:

381596

AN:

1087767

Hom.:

46031

Cov.:

AF XY:

0.354

AC XY:

125882

AN XY:

355957

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.368

AC:

39606

AN:

107538

Hom.:

6130

Cov.:

AF XY:

0.323

AC XY:

9764

AN XY:

30272

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.376

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.358

Hom.:

3030

Asia WGS

AF:

0.317

AC:

800

AN:

2522

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	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, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 18, 2014	- -
Benign, no assertion criteria provided	clinical testing	Eurofins Ntd Llc (ga)	Aug 15, 2012	- -

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