X-50598413-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_020717.5(SHROOM4):c.4065C>A(p.Ala1355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,207,762 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A1355A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., 9 hem., cov: 22)
  • Exomes 𝑓: 0.000029 (0 hom. 9 hem.)
• Consequence: SHROOM4 NM_020717.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.87

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant X-50598413-G-T is Benign according to our data. Variant chrX-50598413-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.87 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM4	NM_020717.5	c.4065C>A	p.Ala1355=	synonymous_variant	8/9	ENST00000376020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM4	ENST00000376020.9	c.4065C>A	p.Ala1355=	synonymous_variant	8/9	2	NM_020717.5	P1
SHROOM4	ENST00000289292.11	c.4065C>A	p.Ala1355=	synonymous_variant	8/10	1		P1
SHROOM4	ENST00000460112.3	c.3717C>A	p.Ala1239=	synonymous_variant	7/8	5

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 25 AN: 111540 Hom.: 0 Cov.: 22 AF XY: 0.000267 AC XY: 9 AN XY: 33722

Gnomad AFR AF: 0.000620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000381

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00133

GnomAD3 exomes AF: 0.0000960 AC: 17 AN: 177128 Hom.: 0 AF XY: 0.0000806 AC XY: 5 AN XY: 62022

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.000111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.0000292 AC: 32 AN: 1096169 Hom.: 0 Cov.: 32 AF XY: 0.0000249 AC XY: 9 AN XY: 361653

Gnomad4 AFR exome AF: 0.000910

Gnomad4 AMR exome AF: 0.000171

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: 0.00

Gnomad4 OTH exome AF: 0.0000435

GnomAD4 genome AF: 0.000224 AC: 25 AN: 111593 Hom.: 0 Cov.: 22 AF XY: 0.000266 AC XY: 9 AN XY: 33785

Gnomad4 AFR AF: 0.000619

Gnomad4 AMR AF: 0.000381

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00131

Bravo AF: 0.000382

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

SHROOM4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.084
Dann	Benign	0.48

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: rs140760349; hg19: chrX-50341413;