rs143151534

Positions:

• chrX-50607728-TTCCTCC-T
• chrX-50607728-TTCCTCC-TTCC
• chrX-50607728-TTCCTCC-TTCCTCCTCC
• chrX-50607728-TTCCTCC-TTCCTCCTCCTCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020717.5(SHROOM4):​c.3408_3413del​(p.Glu1150_Glu1151del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,116,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., 4 hem., cov: 14)
  • Exomes 𝑓: 0.00016 (0 hom. 46 hem.)
• Consequence: SHROOM4 NM_020717.5 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.3408_3413del	p.Glu1150_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	c.3408_3413del	p.Glu1150_Glu1151del	inframe_deletion	6/9	2	NM_020717.5	ENSP00000365188	P1
SHROOM4	ENST00000289292.11	c.3408_3413del	p.Glu1150_Glu1151del	inframe_deletion	6/10	1		ENSP00000289292	P1
SHROOM4	ENST00000460112.3	c.3060_3065del	p.Glu1034_Glu1035del	inframe_deletion	5/8	5		ENSP00000421450

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 15 AN: 105682 Hom.: 0 Cov.: 14 AF XY: 0.000139 AC XY: 4 AN XY: 28690

Gnomad AFR AF: 0.0000705

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000297

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000214

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000134 AC: 17 AN: 127114 Hom.: 0 AF XY: 0.0000919 AC XY: 3 AN XY: 32658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000882

Gnomad FIN exome AF: 0.0000829

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000157 AC: 159 AN: 1010981 Hom.: 0 AF XY: 0.000151 AC XY: 46 AN XY: 304927

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000195

Gnomad4 OTH exome AF: 0.000187

GnomAD4 genome AF: 0.000142 AC: 15 AN: 105682 Hom.: 0 Cov.: 14 AF XY: 0.000139 AC XY: 4 AN XY: 28690

Gnomad4 AFR AF: 0.0000705

Gnomad4 AMR AF: 0.000101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000297

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000214

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000136

ClinVar

Not reported in ClinVar

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: rs143151534; hg19: chrX-50350728;