Variant X-100650877-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014467.3(SRPX2):c.163+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,192,175 control chromosomes in the GnomAD database, including 132 homozygotes. There are 1,355 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 79 hom., 635 hem., cov: 22)

Exomes 𝑓: 0.0025 ( 53 hom. 720 hem. )

Consequence

SRPX2
NM_014467.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-100650877-T-C is Benign according to our data. Variant chrX-100650877-T-C is described in ClinVar as [Benign]. Clinvar id is 139327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-100650877-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3 linkuse as main transcript	c.163+12T>C		intron_variant		ENST00000373004.5	NP_055282.1	O60687

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5 linkuse as main transcript	c.163+12T>C		intron_variant		1	NM_014467.3	ENSP00000362095.3		O60687

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

2403

AN:

111480

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

633

AN XY:

33640

show subpopulations

Gnomad AFR

AF:

0.0744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00846

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000388

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000282

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00624

AC:

1135

AN:

181861

Hom.:

AF XY:

0.00423

AC XY:

281

AN XY:

66403

show subpopulations

Gnomad AFR exome

AF:

0.0760

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000160

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00254

AC:

2750

AN:

1080637

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

720

AN XY:

346859

show subpopulations

Gnomad4 AFR exome

AF:

0.0814

Gnomad4 AMR exome

AF:

0.00486

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000448

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.0216

AC:

2408

AN:

111538

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

635

AN XY:

33706

show subpopulations

Gnomad4 AFR

AF:

0.0744

Gnomad4 AMR

AF:

0.00845

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000389

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000282

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 31, 2013	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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.6

DANN

Benign

0.60

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