X-100661173-T-A

Variant names:

• chrX-100661173-T-A
• rs36224184
• NM_014467.3:c.164-1003T>A

Variant summary

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

The NM_014467.3(SRPX2):​c.164-1003T>A 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 112,359 control chromosomes in the GnomAD database, including 113 homozygotes. There are 1,142 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., 1142 hem., cov: 24)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014467.3. 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.164-1003T>A		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.164-1003T>A		intron	N/A	ENSP00000362095.3
	SRPX2	ENST00000638458.1	TSL:5	c.164-979T>A		intron	N/A	ENSP00000492168.1
	SRPX2	ENST00000640889.1	TSL:5	c.164-1003T>A		intron	N/A	ENSP00000492571.1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 4289 AN: 112305 Hom.: 113 Cov.: 24

Gnomad AFR AF: 0.00831

Gnomad AMI AF: 0.00871

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0264

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

GnomAD4 genome AF: 0.0382 AC: 4289 AN: 112359 Hom.: 113 Cov.: 24 AF XY: 0.0331 AC XY: 1142 AN XY: 34533

African (AFR) AF: 0.00830 AC: 257 AN: 30980

American (AMR) AF: 0.0210 AC: 224 AN: 10689

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 97 AN: 2650

East Asian (EAS) AF: 0.00195 AC: 7 AN: 3583

South Asian (SAS) AF: 0.0201 AC: 54 AN: 2688

European-Finnish (FIN) AF: 0.0285 AC: 175 AN: 6136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0645 AC: 3429 AN: 53193

Other (OTH) AF: 0.0261 AC: 40 AN: 1533

Alfa AF: 0.0546 Hom.: 284

Bravo AF: 0.0354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.077
DANN	Benign	0.69
PhyloP100		-0.40
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: rs36224184; hg19: chrX-99916170;