Variant X-38160076-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006307.5(SRPX):c.896G>T(p.Ser299Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,210,174 control chromosomes in the GnomAD database, including 1 homozygotes. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000070 ( 1 hom. 25 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096001595).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX	NM_006307.5 link	c.896G>T	p.Ser299Ile	missense_variant	Exon 7 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.896G>T	p.Ser299Ile	missense_variant	Exon 7 of 10	1	NM_006307.5	ENSP00000367794.3		P78539-1
ENSG00000250349	ENST00000465127.1 link	c.172-506045C>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

112613

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

34745

show subpopulations

Gnomad AFR

AF:

0.00132

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:

0.00131

GnomAD3 exomes

AF:

0.000183

AC:

AN:

180246

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

65032

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000539

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000702

AC:

AN:

1097508

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

362930

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000713

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000382

AC:

AN:

112666

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

34808

show subpopulations

Gnomad4 AFR

AF:

0.00132

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:

0.00129

Alfa

AF:

0.0000593

Hom.:

Bravo

AF:

0.000589

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.896G>T (p.S299I) alteration is located in exon 7 (coding exon 7) of the SRPX gene. This alteration results from a G to T substitution at nucleotide position 896, causing the serine (S) at amino acid position 299 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;.;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

T;D;D;D

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.096

T;T;T;T

MetaSVM

Uncertain

0.025

MutationAssessor

Uncertain

2.9

.;.;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Uncertain

0.50

Sift

Benign

0.055

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

1.0

.;.;.;D

Vest4

0.49

MVP

0.97

MPC

0.16

ClinPred

0.11

GERP RS

5.7

Varity_R

0.65

gMVP

0.80

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