X-100650685-T-C

Position:

• chrX-100650685-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014467.3(SRPX2):​c.83-100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 769,784 control chromosomes in the GnomAD database, including 652 homozygotes. There are 8,106 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (200 hom., 1663 hem., cov: 22)
  • Exomes 𝑓: 0.027 (452 hom. 6443 hem.)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-100650685-T-C is Benign according to our data. Variant chrX-100650685-T-C is described in ClinVar as [Benign]. Clinvar id is 1239134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.83-100T>C		intron_variant		ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.83-100T>C		intron_variant		1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 5442 AN: 111062 Hom.: 200 Cov.: 22 AF XY: 0.0498 AC XY: 1656 AN XY: 33274

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00741

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0271 AC: 17819 AN: 658667 Hom.: 452 AF XY: 0.0345 AC XY: 6443 AN XY: 186561

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0468

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0559

Gnomad4 NFE exome AF: 0.00597

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.0491 AC: 5455 AN: 111117 Hom.: 200 Cov.: 22 AF XY: 0.0499 AC XY: 1663 AN XY: 33339

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.0148

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.00741

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0176 Hom.: 1042

Bravo AF: 0.0526

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2073164; hg19: chrX-99905682;