rs540437538

chrX-50627692-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020717.5(SHROOM4):c.2896-17A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,193,028 control chromosomes in the GnomAD database, including 1 homozygotes. There are 292 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00047 (1 hom. 286 hem.)
• Consequence: SHROOM4 NM_020717.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.212

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-50627692-T-C is Benign according to our data. Variant chrX-50627692-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 212179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM4	NM_020717.5	c.2896-17A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000376020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM4	ENST00000376020.9	c.2896-17A>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_020717.5	P1
SHROOM4	ENST00000289292.11	c.2896-17A>G		splice_polypyrimidine_tract_variant, intron_variant		1		P1
SHROOM4	ENST00000460112.3	c.2548-17A>G		splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000242 AC: 27 AN: 111783 Hom.: 0 Cov.: 23 AF XY: 0.000177 AC XY: 6 AN XY: 33955

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00949

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.000665

GnomAD3 exomes AF: 0.000908 AC: 165 AN: 181681 Hom.: 1 AF XY: 0.00113 AC XY: 75 AN XY: 66251

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: 0.00877

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000472 AC: 510 AN: 1081191 Hom.: 1 Cov.: 28 AF XY: 0.000823 AC XY: 286 AN XY: 347301

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000568

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00880

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000847

Gnomad4 OTH exome AF: 0.000637

GnomAD4 genome AF: 0.000241 AC: 27 AN: 111837 Hom.: 0 Cov.: 23 AF XY: 0.000176 AC XY: 6 AN XY: 34019

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00952

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.000657

Bravo AF: 0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 11, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.89
Dann	Benign	0.59

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: rs540437538; hg19: chrX-50370692;