Variant rs138091242 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014467.3(SRPX2):c.1293C>T(p.Tyr431Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,209,709 control chromosomes in the GnomAD database, including 8 homozygotes. There are 192 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 0.00068 ( 0 hom., 23 hem., cov: 23)

Exomes 𝑓: 0.00046 ( 8 hom. 169 hem. )

Consequence

SRPX2
NM_014467.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.05

Variant links:

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 links:

SRPX2 (HGNC:):

SRPX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant X-100670882-C-T is Benign according to our data. Variant chrX-100670882-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 139326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-100670882-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3 linkuse as main transcript	c.1293C>T	p.Tyr431Tyr	synonymous_variant	11/11	ENST00000373004.5	NP_055282.1	O60687

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRPX2	ENST00000373004.5 linkuse as main transcript	c.1293C>T	p.Tyr431Tyr	synonymous_variant	11/11	1	NM_014467.3	ENSP00000362095.3	O60687
SRPX2	ENST00000640282.1 linkuse as main transcript	c.*28C>T		3_prime_UTR_variant	3/3	5		ENSP00000491188.1	A0A1W2PNZ6
SRPX2	ENST00000638920.1 linkuse as main transcript	n.1296C>T		non_coding_transcript_exon_variant	10/10	5

Frequencies

GnomAD3 genomes

AF:

0.000691

AC:

AN:

111480

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

33670

show subpopulations

Gnomad AFR

AF:

0.000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000570

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0163

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000673

GnomAD3 exomes

AF:

0.00125

AC:

229

AN:

183440

Hom.:

AF XY:

0.000987

AC XY:

AN XY:

67878

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.000839

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000455

AC:

500

AN:

1098172

Hom.:

Cov.:

AF XY:

0.000465

AC XY:

169

AN XY:

363526

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00917

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000178

Gnomad4 OTH exome

AF:

0.00317

GnomAD4 genome

AF:

0.000681

AC:

AN:

111537

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

AN XY:

33737

show subpopulations

Gnomad4 AFR

AF:

0.000261

Gnomad4 AMR

AF:

0.000570

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0161

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.000664

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 06, 2014	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. -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 22, 2017	- -

Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.8

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over