rs5920840

Variant names:

• chrX-100661597-T-C
• rs5920840
• NM_014467.3:c.164-579T>C

Variant summary

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

The ENST00000373004.5(SRPX2):​c.164-579T>C 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 0.78 (24057 hom., 24870 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: SRPX2 ENST00000373004.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• 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=-1.03).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373004.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	NM_014467.3	MANE Select	c.164-579T>C		intron	N/A	NP_055282.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	ENST00000373004.5	TSL:1 MANE Select	c.164-579T>C		intron	N/A	ENSP00000362095.3
	SRPX2	ENST00000638458.1	TSL:5	c.164-555T>C		intron	N/A	ENSP00000492168.1
	SRPX2	ENST00000640889.1	TSL:5	c.164-579T>C		intron	N/A	ENSP00000492571.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 85373 AN: 109920 Hom.: 24070 Cov.: 22

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.781

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: 0.776 AC: 85388 AN: 109968 Hom.: 24057 Cov.: 22 AF XY: 0.772 AC XY: 24870 AN XY: 32224

African (AFR) AF: 0.611 AC: 18429 AN: 30178

American (AMR) AF: 0.746 AC: 7710 AN: 10337

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 2405 AN: 2632

East Asian (EAS) AF: 0.734 AC: 2569 AN: 3499

South Asian (SAS) AF: 0.678 AC: 1713 AN: 2526

European-Finnish (FIN) AF: 0.884 AC: 5011 AN: 5667

Middle Eastern (MID) AF: 0.875 AC: 189 AN: 216

European-Non Finnish (NFE) AF: 0.865 AC: 45610 AN: 52754

Other (OTH) AF: 0.779 AC: 1159 AN: 1488

Alfa AF: 0.820 Hom.: 6977

Bravo AF: 0.763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.25
PhyloP100		-0.51
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: rs5920840; hg19: chrX-99916594;