rs201922875

chrX-50607758-C-CTGCTGCTGCTGTchrX-50607758-C-CTGCTGCTGCTGTTGCTGCTGCTGTTGCTGCTTCTGCTGCTGCTGTchrX-50607758-C-CTGCTGCTGCTGTTGCTGCTGT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_020717.5(SHROOM4):c.3383_3384insACAGCAGCAGCA(p.Gln1125_Gln1128dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q1128Q) has been classified 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 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.676

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]

ACMG classification

Verdict is Benign. Variant got -12 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.
• BS2: High Homozygotes in GnomAd at 6135 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM4	NM_020717.5	c.3383_3384insACAGCAGCAGCA	p.Gln1125_Gln1128dup	inframe_insertion	6/9	ENST00000376020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM4	ENST00000376020.9	c.3383_3384insACAGCAGCAGCA	p.Gln1125_Gln1128dup	inframe_insertion	6/9	2	NM_020717.5	P1
SHROOM4	ENST00000289292.11	c.3383_3384insACAGCAGCAGCA	p.Gln1125_Gln1128dup	inframe_insertion	6/10	1		P1
SHROOM4	ENST00000460112.3	c.3035_3036insACAGCAGCAGCA	p.Gln1009_Gln1012dup	inframe_insertion	5/8	5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 39596 AN: 107497 Hom.: 6135 Cov.: 0 AF XY: 0.322 AC XY: 9739 AN XY: 30221

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

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.: 33 AF XY: 0.354 AC XY: 125882 AN XY: 355957

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.: 0 AF XY: 0.323 AC XY: 9764 AN XY: 30272

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

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201922875; hg19: chrX-50350758;