rs17329105

Variant names:

• chrX-100659298-G-A
• rs17329105
• NM_014467.3:c.164-2878G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-100659298-G-A
• chrX-100659298-G-C

Variant summary

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

The NM_014467.3(SRPX2):​c.164-2878G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 111,669 control chromosomes in the GnomAD database, including 466 homozygotes. There are 2,960 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 0.085 (466 hom., 2960 hem., cov: 23)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 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.164-2878G>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.164-2878G>A		intron	N/A	ENSP00000362095.3
	SRPX2	ENST00000638458.1	TSL:5	c.164-2854G>A		intron	N/A	ENSP00000492168.1
	SRPX2	ENST00000640889.1	TSL:5	c.164-2878G>A		intron	N/A	ENSP00000492571.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 9449 AN: 111617 Hom.: 465 Cov.: 23

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0424

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0848 AC: 9469 AN: 111669 Hom.: 466 Cov.: 23 AF XY: 0.0874 AC XY: 2960 AN XY: 33869

African (AFR) AF: 0.116 AC: 3579 AN: 30773

American (AMR) AF: 0.170 AC: 1791 AN: 10541

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 97 AN: 2649

East Asian (EAS) AF: 0.260 AC: 915 AN: 3523

South Asian (SAS) AF: 0.210 AC: 555 AN: 2647

European-Finnish (FIN) AF: 0.0761 AC: 457 AN: 6004

Middle Eastern (MID) AF: 0.0512 AC: 11 AN: 215

European-Non Finnish (NFE) AF: 0.0358 AC: 1903 AN: 53114

Other (OTH) AF: 0.106 AC: 161 AN: 1515

Alfa AF: 0.0605 Hom.: 3335

Bravo AF: 0.0975

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-0.86
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: rs17329105; hg19: chrX-99914295;