X-100651156-T-G

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.163+291T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 326,104 control chromosomes in the GnomAD database, including 414 homozygotes. There are 3,924 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (202 hom., 1671 hem., cov: 22)
  • Exomes 𝑓: 0.033 (212 hom. 2253 hem.)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.551

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=-0.59).
• BP6: Variant X-100651156-T-G is Benign according to our data. Variant chrX-100651156-T-G is described in ClinVar as [Benign]. Clinvar id is 1247373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPX2	NM_014467.3	c.163+291T>G		intron_variant		ENST00000373004.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPX2	ENST00000373004.5	c.163+291T>G		intron_variant		1	NM_014467.3	P1

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 5379 AN: 111235 Hom.: 201 Cov.: 22 AF XY: 0.0497 AC XY: 1663 AN XY: 33455

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.0210

Gnomad NFE AF: 0.00737

Gnomad OTH AF: 0.0340

GnomAD4 exome AF: 0.0327 AC: 7033 AN: 214814 Hom.: 212 AF XY: 0.0435 AC XY: 2253 AN XY: 51794

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.0146

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0548

Gnomad4 NFE exome AF: 0.00683

Gnomad4 OTH exome AF: 0.0303

GnomAD4 genome AF: 0.0485 AC: 5394 AN: 111290 Hom.: 202 Cov.: 22 AF XY: 0.0499 AC XY: 1671 AN XY: 33520

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.0148

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0598

Gnomad4 NFE AF: 0.00737

Gnomad4 OTH AF: 0.0368

Alfa AF: 0.0315 Hom.: 151

Bravo AF: 0.0517

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

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	3.3
Dann	Benign	0.90

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: rs2073165; hg19: chrX-99906153;