X-38160076-C-T

Variant names:

• chrX-38160076-C-T
• rs140816750
• NM_006307.5:c.896G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006307.5(SRPX):​c.896G>A​(p.Ser299Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX	NM_006307.5	c.896G>A	p.Ser299Asn	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.896G>A	p.Ser299Asn	missense_variant	Exon 7 of 10	1	NM_006307.5	ENSP00000367794.3
ENSG00000250349	ENST00000465127.1	c.172-506045C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097508 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362930

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;.;.;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.61	T;T;D;D
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.6	.;.;L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.051	T;D;T;D
Sift4G	Benign	0.094	T;T;T;T
Polyphen		1.0	.;.;.;D
Vest4		0.70
MutPred		0.67		.;.;Loss of phosphorylation at S299 (P = 0.2053);Loss of phosphorylation at S299 (P = 0.2053);
MVP		0.90
MPC		0.15
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.64
gMVP		0.65

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: rs140816750; hg19: chrX-38019329;