chrX-50607728-TTCC-T

Variant names:

• chrX-50607728-TTCC-T
• rs143151534
• NM_020717.5:c.3411_3413delGGA

Variant summary

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

The NM_020717.5(SHROOM4):​c.3411_3413delGGA​(p.Glu1138del) variant causes a disruptive 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 Likely 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 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.943

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-50607728-TTCC-T is Benign according to our data. Variant chrX-50607728-TTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 590248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.3411_3413delGGA	p.Glu1138del	disruptive_inframe_deletion	Exon 6 of 9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.3411_3413delGGA	p.Glu1138del	disruptive_inframe_deletion	Exon 6 of 9	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.3411_3413delGGA	p.Glu1138del	disruptive_inframe_deletion	Exon 6 of 10	1		ENSP00000289292.7
SHROOM4	ENST00000460112.3	c.3063_3065delGGA	p.Glu1022del	disruptive_inframe_deletion	Exon 5 of 8	5		ENSP00000421450.1

Frequencies

GnomAD3 genomes AF: 0.000426 AC: 45 AN: 105667 Hom.: 0 Cov.: 14 AF XY: 0.000349 AC XY: 10 AN XY: 28681

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: 76 AN: 127114 Hom.: 0 AF XY: 0.000184 AC XY: 6 AN XY: 32658

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.: 0 AF XY: 0.000179 AC XY: 54 AN XY: 301399

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: 45 AN: 105703 Hom.: 0 Cov.: 14 AF XY: 0.000348 AC XY: 10 AN XY: 28729

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/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 10, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Mar 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SHROOM4: BS2 -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs143151534; hg19: chrX-50350728;