Variant X-38160977-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3PP5BS2

The NM_006307.5(SRPX):c.731G>C(p.Arg244Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000439 in 1,206,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000047 ( 0 hom. 17 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.06

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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.818

PP5

Variant X-38160977-C-G is Pathogenic according to our data. Variant chrX-38160977-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 599603.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX	NM_006307.5 linkuse as main transcript	c.731G>C	p.Arg244Thr	missense_variant	6/10	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.731G>C	p.Arg244Thr	missense_variant	6/10	1	NM_006307.5	ENSP00000367794	P2	P78539-1
SRPX	ENST00000544439.5 linkuse as main transcript	c.671G>C	p.Arg224Thr	missense_variant	5/9	2		ENSP00000440758	A2	P78539-5
SRPX	ENST00000432886.6 linkuse as main transcript	c.554G>C	p.Arg185Thr	missense_variant	5/9	2		ENSP00000411165		P78539-3
SRPX	ENST00000538295.5 linkuse as main transcript	c.731G>C	p.Arg244Thr	missense_variant	6/9	2		ENSP00000445034		P78539-4

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33624

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183030

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000475

AC:

AN:

1095476

Hom.:

Cov.:

AF XY:

0.0000471

AC XY:

AN XY:

361028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000595

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33624

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Short stature

Pathogenic:1

Likely pathogenic, no assertion criteria provided

case-control

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Nov 18, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

.;.;.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Pathogenic

0.62

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.067

T;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

1.0

.;.;.;D

Vest4

0.83

MutPred

0.67

.;.;Loss of MoRF binding (P = 0.0278);Loss of MoRF binding (P = 0.0278);

MVP

0.91

MPC

0.17

ClinPred

0.67

GERP RS

5.9

Varity_R

0.80

gMVP

0.77

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