chrX-100660565-C-T

Variant names:

• chrX-100660565-C-T
• rs36224192
• NM_014467.3:c.164-1611C>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.164-1611C>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 0.64 (17126 hom., 20749 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 0 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.164-1611C>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.164-1611C>T		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 70511 AN: 110485 Hom.: 17139 Cov.: 23

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.674

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: 0.638 AC: 70515 AN: 110537 Hom.: 17126 Cov.: 23 AF XY: 0.629 AC XY: 20749 AN XY: 32977

African (AFR) AF: 0.376 AC: 11440 AN: 30426

American (AMR) AF: 0.660 AC: 6892 AN: 10436

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2110 AN: 2625

East Asian (EAS) AF: 0.578 AC: 2029 AN: 3508

South Asian (SAS) AF: 0.519 AC: 1378 AN: 2653

European-Finnish (FIN) AF: 0.698 AC: 4031 AN: 5774

Middle Eastern (MID) AF: 0.808 AC: 173 AN: 214

European-Non Finnish (NFE) AF: 0.776 AC: 40885 AN: 52718

Other (OTH) AF: 0.670 AC: 1010 AN: 1507

Alfa AF: 0.701 Hom.: 5663

Bravo AF: 0.628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.84
PhyloP100		0.57
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: rs36224192; hg19: chrX-99915562;