Variant X-38160034-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_006307.5(SRPX):c.938C>T(p.Thr313Met) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,209,442 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00010 ( 0 hom. 39 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11757299).

BP6

Variant X-38160034-G-A is Benign according to our data. Variant chrX-38160034-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2660289.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX	NM_006307.5 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	7/10	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.938C>T	p.Thr313Met	missense_variant	7/10	1	NM_006307.5	ENSP00000367794	P2	P78539-1

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

112568

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34702

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000935

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

176987

Hom.:

AF XY:

0.000128

AC XY:

AN XY:

62267

show subpopulations

Gnomad AFR exome

AF:

0.0000785

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000276

Gnomad FIN exome

AF:

0.000131

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.000105

AC:

115

AN:

1096820

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

362318

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000130

Gnomad4 FIN exome

AF:

0.0000990

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.000133

AC:

AN:

112622

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34766

show subpopulations

Gnomad4 AFR

AF:

0.000194

Gnomad4 AMR

AF:

0.0000934

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000181

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.938C>T (p.T313M) alteration is located in exon 7 (coding exon 7) of the SRPX gene. This alteration results from a C to T substitution at nucleotide position 938, causing the threonine (T) at amino acid position 313 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

SRPX: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;.;.;T

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

T;D;D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

.;.;M;M

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.030

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.67

.;.;.;P

Vest4

0.14

MVP

0.95

MPC

0.036

ClinPred

0.053

GERP RS

3.9

Varity_R

0.068

gMVP

0.38

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