rs10521492

Variant names:

• chrX-100663669-C-T
• rs10521492
• NM_014467.3:c.356-1105C>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.356-1105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 112,397 control chromosomes in the GnomAD database, including 320 homozygotes. There are 1,930 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 0.057 (320 hom., 1930 hem., cov: 23)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.356-1105C>T		intron_variant	Intron 4 of 10	ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.356-1105C>T		intron_variant	Intron 4 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 6364 AN: 112345 Hom.: 319 Cov.: 23

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0568 AC: 6380 AN: 112397 Hom.: 320 Cov.: 23 AF XY: 0.0558 AC XY: 1930 AN XY: 34569

African (AFR) AF: 0.150 AC: 4620 AN: 30899

American (AMR) AF: 0.0383 AC: 409 AN: 10668

Ashkenazi Jewish (ASJ) AF: 0.0238 AC: 63 AN: 2649

East Asian (EAS) AF: 0.133 AC: 473 AN: 3548

South Asian (SAS) AF: 0.143 AC: 386 AN: 2699

European-Finnish (FIN) AF: 0.00857 AC: 53 AN: 6183

Middle Eastern (MID) AF: 0.0183 AC: 4 AN: 219

European-Non Finnish (NFE) AF: 0.00587 AC: 313 AN: 53301

Other (OTH) AF: 0.0383 AC: 59 AN: 1542

Alfa AF: 0.0300 Hom.: 348

Bravo AF: 0.0621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.27
PhyloP100		-1.5
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: rs10521492; hg19: chrX-99918666;