chrX-100646647-C-T

Variant names:

• chrX-100646647-C-T
• rs56259360
• NM_014467.3:c.82+243C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014467.3(SRPX2):​c.82+243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 112,017 control chromosomes in the GnomAD database, including 36 homozygotes. There are 614 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (36 hom., 614 hem., cov: 23)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.524
• 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-100646647-C-T is Benign according to our data. Variant chrX-100646647-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 677499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0202 (2264/112017) while in subpopulation NFE AF = 0.0298 (1587/53187). AF 95% confidence interval is 0.0286. There are 36 homozygotes in GnomAd4. There are 614 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2264 XL,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	NM_014467.3	MANE Select	c.82+243C>T		intron	N/A	NP_055282.1	O60687

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	ENST00000373004.5	TSL:1 MANE Select	c.82+243C>T		intron	N/A	ENSP00000362095.3	O60687
	SRPX2	ENST00000638458.1	TSL:5	c.82+243C>T		intron	N/A	ENSP00000492168.1	A0A1W2PR88
	SRPX2	ENST00000640889.1	TSL:5	c.82+243C>T		intron	N/A	ENSP00000492571.1	A0A1W2PRB1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2266 AN: 111964 Hom.: 37 Cov.: 23

Gnomad AFR AF: 0.00503

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00298

Gnomad FIN AF: 0.00709

Gnomad MID AF: 0.0596

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0324

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

GnomAD4 genome AF: 0.0202 AC: 2264 AN: 112017 Hom.: 36 Cov.: 23 AF XY: 0.0180 AC XY: 614 AN XY: 34197

African (AFR) AF: 0.00501 AC: 155 AN: 30909

American (AMR) AF: 0.0218 AC: 230 AN: 10555

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 100 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3549

South Asian (SAS) AF: 0.00337 AC: 9 AN: 2673

European-Finnish (FIN) AF: 0.00709 AC: 43 AN: 6066

Middle Eastern (MID) AF: 0.0514 AC: 11 AN: 214

European-Non Finnish (NFE) AF: 0.0298 AC: 1587 AN: 53187

Other (OTH) AF: 0.0320 AC: 49 AN: 1531

Alfa AF: 0.0241 Hom.: 144

Bravo AF: 0.0211

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.52
PromoterAI		-0.020	Neutral
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: rs56259360; hg19: chrX-99901644;