rs10521492

Positions:

• chrX-100663669-C-T

Variant summary

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

The NM_014467.3(SRPX2):​c.356-1105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 112,397 control chromosomes in the GnomAD database, including 320 homozygotes. There are 1,930 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 0.057 (320 hom., 1930 hem., cov: 23)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.356-1105C>T		intron_variant		ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.356-1105C>T		intron_variant		1	NM_014467.3	ENSP00000362095	P1

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 6364 AN: 112345 Hom.: 319 Cov.: 23 AF XY: 0.0556 AC XY: 1920 AN XY: 34507

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0568 AC: 6380 AN: 112397 Hom.: 320 Cov.: 23 AF XY: 0.0558 AC XY: 1930 AN XY: 34569

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0238

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.00587

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0307 Hom.: 301

Bravo AF: 0.0621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.27

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: rs10521492; hg19: chrX-99918666;