X-100661311-C-T

Variant names:

• chrX-100661311-C-T
• rs5921619
• NM_014467.3:c.164-865C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014467.3(SRPX2):​c.164-865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.89 (30759 hom., 28942 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 1 publications found

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]

SRPX2 Gene-Disease associations (from GenCC):

• rolandic epilepsy-speech dyspraxia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• polymicrogyria, bilateral perisylvian, X-linked

  Inheritance: XL Classification: LIMITED Submitted by: G2P
• rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

  Inheritance: XL Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.164-865C>T		intron_variant	Intron 3 of 10	ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.164-865C>T		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.886 AC: 98007 AN: 110660 Hom.: 30766 Cov.: 23

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.920

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.910

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.886 AC: 98046 AN: 110711 Hom.: 30759 Cov.: 23 AF XY: 0.880 AC XY: 28942 AN XY: 32907

African (AFR) AF: 0.843 AC: 25646 AN: 30410

American (AMR) AF: 0.921 AC: 9603 AN: 10425

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 2333 AN: 2633

East Asian (EAS) AF: 0.854 AC: 2997 AN: 3509

South Asian (SAS) AF: 0.828 AC: 2151 AN: 2598

European-Finnish (FIN) AF: 0.821 AC: 4692 AN: 5714

Middle Eastern (MID) AF: 0.931 AC: 201 AN: 216

European-Non Finnish (NFE) AF: 0.913 AC: 48397 AN: 53012

Other (OTH) AF: 0.908 AC: 1370 AN: 1509

Alfa AF: 0.903 Hom.: 98444

Bravo AF: 0.892

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.44
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5921619; hg19: chrX-99916308;