rs5921620

Positions:

• chrX-100664479-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014467.3(SRPX2):​c.356-295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 110,198 control chromosomes in the GnomAD database, including 3,950 homozygotes. There are 9,660 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (3950 hom., 9660 hem., cov: 22)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

Genes affected

SRPX2 (HGNC:30668): (sushi repeat containing protein X-linked 2) This gene encodes a secreted protein that contains three sushi repeat motifs. The encoded protein may play a role in the development of speech and language centers in the brain. This protein may also be involved in angiogenesis. Mutations in this gene are the cause of bilateral perisylvian polymicrogyria, rolandic epilepsy, speech dyspraxia and cognitive disability. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-100664479-T-C is Benign according to our data. Variant chrX-100664479-T-C is described in ClinVar as [Benign]. Clinvar id is 668969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.356-295T>C		intron_variant		ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.356-295T>C		intron_variant		1	NM_014467.3	ENSP00000362095	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 32658 AN: 110144 Hom.: 3939 Cov.: 22 AF XY: 0.296 AC XY: 9621 AN XY: 32456

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 32711 AN: 110198 Hom.: 3950 Cov.: 22 AF XY: 0.297 AC XY: 9660 AN XY: 32520

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.299

Alfa AF: 0.226 Hom.: 12371

Bravo AF: 0.313

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.67

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: rs5921620; hg19: chrX-99919476;