chrX-38160939-C-T

Variant names:

• chrX-38160939-C-T
• rs201000269
• NM_006307.5:c.769G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006307.5(SRPX):​c.769G>A​(p.Val257Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX	NM_006307.5	c.769G>A	p.Val257Ile	missense_variant	Exon 6 of 10	ENST00000378533.4	NP_006298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4	c.769G>A	p.Val257Ile	missense_variant	Exon 6 of 10	1	NM_006307.5	ENSP00000367794.3
ENSG00000250349	ENST00000465127.1	c.172-505182C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	.;.;.;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	.;.;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.83	N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.025	D;D;D;D
Sift4G	Benign	0.22	T;T;T;T
Polyphen		1.0	.;.;.;D
Vest4		0.61
MutPred		0.88		.;.;Loss of methylation at K256 (P = 0.0625);Loss of methylation at K256 (P = 0.0625);
MVP		0.57
MPC		0.15
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.41
gMVP		0.48

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

Other links and lift over

dbSNP: rs201000269; hg19: chrX-38020192;