Variant X-38154583-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000378533.4(SRPX):c.1090C>A(p.Gln364Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,205,933 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000099 ( 0 hom. 34 hem. )

Consequence

SRPX
ENST00000378533.4 missense, splice_region

Scores

Splicing: ADA: 0.8577

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34780177).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX	NM_006307.5 linkuse as main transcript	c.1090C>A	p.Gln364Lys	missense_variant, splice_region_variant	9/10	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.1090C>A	p.Gln364Lys	missense_variant, splice_region_variant	9/10	1	NM_006307.5	ENSP00000367794	P2	P78539-1

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

111660

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33814

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000473

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:

0.000113

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.0000693

AC:

AN:

173271

Hom.:

AF XY:

0.0000683

AC XY:

AN XY:

58575

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

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:

0.000104

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000987

AC:

108

AN:

1094273

Hom.:

Cov.:

AF XY:

0.0000945

AC XY:

AN XY:

359967

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000116

AC:

AN:

111660

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33814

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.000473

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.000664

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1090C>A (p.Q364K) alteration is located in exon 9 (coding exon 9) of the SRPX gene. This alteration results from a C to A substitution at nucleotide position 1090, causing the glutamine (Q) at amino acid position 364 to be replaced by a lysine (K). 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

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

.;.;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.84

.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.63

.;.;P

Vest4

0.42

MVP

0.79

MPC

0.075

ClinPred

0.087

GERP RS

5.6

Varity_R

0.61

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.86

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.020

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