dbSNP rs149411980: SRPX:p.Met395Leu (chrX-38154490-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006307.5(SRPX):c.1183A>T(p.Met395Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,204,472 control chromosomes in the GnomAD database, including 2 homozygotes. There are 65 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., 33 hem., cov: 23)

Exomes 𝑓: 0.00010 ( 0 hom. 32 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

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:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074609816).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX	NM_006307.5 link	c.1183A>T	p.Met395Leu	missense_variant	Exon 9 of 10	ENST00000378533.4	NP_006298.1	P78539-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4 link	c.1183A>T	p.Met395Leu	missense_variant	Exon 9 of 10	1	NM_006307.5	ENSP00000367794.3		P78539-1
ENSG00000250349	ENST00000465127.1 link	c.172-511631T>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

130

AN:

111949

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

34097

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000658

GnomAD3 exomes

AF:

0.000296

AC:

AN:

168676

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

55124

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

114

AN:

1092470

Hom.:

Cov.:

AF XY:

0.0000892

AC XY:

AN XY:

358704

show subpopulations

Gnomad4 AFR exome

AF:

0.00376

Gnomad4 AMR exome

AF:

0.0000578

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.00116

AC:

130

AN:

112002

Hom.:

Cov.:

AF XY:

0.000966

AC XY:

AN XY:

34160

show subpopulations

Gnomad4 AFR

AF:

0.00419

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000650

Alfa

AF:

0.0000905

Hom.:

Bravo

AF:

0.00114

ESP6500AA

AF:

0.00391

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000347

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.031

.;.;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

.;.;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.50

N;N;N

REVEL

Benign

0.044

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.29

MutPred

0.41

.;.;Gain of helix (P = 0.0078);

MVP

0.73

MPC

0.019

ClinPred

0.029

GERP RS

5.8

Varity_R

0.26

gMVP

0.36

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