X-100646647-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPX2	NM_014467.3	c.82+243C>T		intron_variant		ENST00000373004.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPX2	ENST00000373004.5	c.82+243C>T		intron_variant		1	NM_014467.3	P1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2266 AN: 111964 Hom.: 37 Cov.: 23 AF XY: 0.0180 AC XY: 613 AN XY: 34134

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

Gnomad4 AFR AF: 0.00501

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00337

Gnomad4 FIN AF: 0.00709

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0320

Alfa AF: 0.0241 Hom.: 144

Bravo AF: 0.0211

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs56259360; hg19: chrX-99901644;