NM_014467.3:c.164-3449C>A

Variant names:

• chrX-100658727-C-A
• rs5966711
• NM_014467.3:c.164-3449C>A

Variant summary

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

The NM_014467.3(SRPX2):​c.164-3449C>A 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 0.75 (22717 hom., 24986 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.164-3449C>A		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.164-3449C>A		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.749 AC: 83186 AN: 110992 Hom.: 22731 Cov.: 23

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.871

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.764

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: 0.749 AC: 83202 AN: 111045 Hom.: 22717 Cov.: 23 AF XY: 0.751 AC XY: 24986 AN XY: 33273

African (AFR) AF: 0.518 AC: 15819 AN: 30512

American (AMR) AF: 0.733 AC: 7648 AN: 10434

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 2429 AN: 2642

East Asian (EAS) AF: 0.733 AC: 2587 AN: 3527

South Asian (SAS) AF: 0.686 AC: 1814 AN: 2643

European-Finnish (FIN) AF: 0.885 AC: 5201 AN: 5875

Middle Eastern (MID) AF: 0.864 AC: 184 AN: 213

European-Non Finnish (NFE) AF: 0.863 AC: 45755 AN: 52995

Other (OTH) AF: 0.762 AC: 1159 AN: 1521

Alfa AF: 0.710 Hom.: 17193

Bravo AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		0.30
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: rs5966711; hg19: chrX-99913724;