rs17329105

chrX-100659298-G-AchrX-100659298-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014467.3(SRPX2):c.164-2878G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 111,669 control chromosomes in the GnomAD database, including 466 homozygotes. There are 2,960 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.085 (466 hom., 2960 hem., cov: 23)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPX2	NM_014467.3	c.164-2878G>A		intron_variant		ENST00000373004.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPX2	ENST00000373004.5	c.164-2878G>A		intron_variant		1	NM_014467.3	P1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 9449 AN: 111617 Hom.: 465 Cov.: 23 AF XY: 0.0872 AC XY: 2948 AN XY: 33807

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0424

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0848 AC: 9469 AN: 111669 Hom.: 466 Cov.: 23 AF XY: 0.0874 AC XY: 2960 AN XY: 33869

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0485 Hom.: 1731

Bravo AF: 0.0975

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.14
Dann	Benign	0.50

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: rs17329105; hg19: chrX-99914295;