Variant rs35318931 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006307.5(SRPX):c.1238C>T(p.Ser413Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,203,841 control chromosomes in the GnomAD database, including 2,529 homozygotes. There are 26,479 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.049 ( 153 hom., 1485 hem., cov: 23)

Exomes 𝑓: 0.073 ( 2376 hom. 24994 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

Variant links:

Genes affected

SRPX (HGNC:11309): (sushi repeat containing protein X-linked) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of cell proliferation involved in contact inhibition; phagolysosome assembly; and positive regulation of extrinsic apoptotic signaling pathway in absence of ligand. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SRPX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008332968).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX	NM_006307.5 linkuse as main transcript	c.1238C>T	p.Ser413Phe	missense_variant	10/10	ENST00000378533.4	NP_006298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4 linkuse as main transcript	c.1238C>T	p.Ser413Phe	missense_variant	10/10	1	NM_006307.5	ENSP00000367794	P2	P78539-1

Frequencies

GnomAD3 genomes

AF:

0.0492

AC:

5491

AN:

111652

Hom.:

153

Cov.:

AF XY:

0.0439

AC XY:

1484

AN XY:

33834

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0491

AC:

8460

AN:

172224

Hom.:

226

AF XY:

0.0483

AC XY:

2783

AN XY:

57616

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.0559

Gnomad NFE exome

AF:

0.0773

Gnomad OTH exome

AF:

0.0540

GnomAD4 exome

AF:

0.0729

AC:

79646

AN:

1092138

Hom.:

2376

Cov.:

AF XY:

0.0698

AC XY:

24994

AN XY:

357868

show subpopulations

Gnomad4 AFR exome

AF:

0.00801

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.0524

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0604

Gnomad4 NFE exome

AF:

0.0851

Gnomad4 OTH exome

AF:

0.0586

GnomAD4 genome

AF:

0.0492

AC:

5493

AN:

111703

Hom.:

153

Cov.:

AF XY:

0.0438

AC XY:

1485

AN XY:

33895

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.0318

Gnomad4 ASJ

AF:

0.0413

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.0115

Gnomad4 FIN

AF:

0.0572

Gnomad4 NFE

AF:

0.0796

Gnomad4 OTH

AF:

0.0401

Alfa

AF:

0.0719

Hom.:

3955

Bravo

AF:

0.0455

TwinsUK

AF:

0.0917

AC:

340

ALSPAC

AF:

0.0886

AC:

256

ESP6500AA

AF:

0.0117

AC:

ESP6500EA

AF:

0.0789

AC:

531

ExAC

AF:

0.0480

AC:

5825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

.;.;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.0017

P;P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.94

.;.;P

Vest4

0.29

MPC

0.12

ClinPred

0.021

GERP RS

5.2

Varity_R

0.31

gMVP

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over