rs41292472

Variant names:

• chrX-100655621-C-T
• rs41292472
• NM_014467.3:c.163+4756C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014467.3(SRPX2):​c.163+4756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 110,627 control chromosomes in the GnomAD database, including 113 homozygotes. There are 1,091 hemizygotes in GnomAD. 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 0.038 (113 hom., 1091 hem., cov: 22)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.163+4756C>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.163+4756C>T		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 4221 AN: 110582 Hom.: 113 Cov.: 22

Gnomad AFR AF: 0.00843

Gnomad AMI AF: 0.0541

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.0387

Gnomad EAS AF: 0.000852

Gnomad SAS AF: 0.0239

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0222

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

GnomAD4 genome AF: 0.0382 AC: 4222 AN: 110627 Hom.: 113 Cov.: 22 AF XY: 0.0332 AC XY: 1091 AN XY: 32877

African (AFR) AF: 0.00841 AC: 256 AN: 30435

American (AMR) AF: 0.0175 AC: 181 AN: 10367

Ashkenazi Jewish (ASJ) AF: 0.0387 AC: 102 AN: 2635

East Asian (EAS) AF: 0.000855 AC: 3 AN: 3510

South Asian (SAS) AF: 0.0244 AC: 63 AN: 2583

European-Finnish (FIN) AF: 0.0322 AC: 188 AN: 5845

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0636 AC: 3359 AN: 52850

Other (OTH) AF: 0.0219 AC: 33 AN: 1504

Alfa AF: 0.0373 Hom.: 612

Bravo AF: 0.0350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		0.15
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: rs41292472; hg19: chrX-99910618;