X-38160141-G-C

Variant names:

• chrX-38160141-G-C
• rs377733865
• NM_006307.5:c.831C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006307.5(SRPX):​c.831C>G​(p.Ser277Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,031 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX	NM_006307.5	c.831C>G	p.Ser277Arg	missense_variant	Exon 7 of 10	ENST00000378533.4	NP_006298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4	c.831C>G	p.Ser277Arg	missense_variant	Exon 7 of 10	1	NM_006307.5	ENSP00000367794.3
ENSG00000250349	ENST00000465127.1	c.172-505980G>C		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000547 AC: 1 AN: 182926 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67436

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: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098031 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363389

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: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;.;.;T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.1	.;.;L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		0.99	.;.;.;D
Vest4		0.38
MutPred		0.56		.;.;Loss of catalytic residue at S277 (P = 0.0782);Loss of catalytic residue at S277 (P = 0.0782);
MVP		0.85
MPC		0.15
ClinPred		0.95	D
GERP RS		-3.9
Varity_R		0.81
gMVP		0.66

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: rs377733865; hg19: chrX-38019394;