chrX-38149868-G-A

Position:

• chrX-38149868-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006307.5(SRPX):​c.1238C>T​(p.Ser413Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,203,841 control chromosomes in the GnomAD database, including 2,529 homozygotes. There are 26,479 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.049 (153 hom., 1485 hem., cov: 23)
  • Exomes 𝑓: 0.073 (2376 hom. 24994 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008332968).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX	NM_006307.5	c.1238C>T	p.Ser413Phe	missense_variant	10/10	ENST00000378533.4	NP_006298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4	c.1238C>T	p.Ser413Phe	missense_variant	10/10	1	NM_006307.5	ENSP00000367794.3
ENSG00000250349	ENST00000465127.1	c.172-516253G>A		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 5491 AN: 111652 Hom.: 153 Cov.: 23 AF XY: 0.0439 AC XY: 1484 AN XY: 33834

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0413

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0406

GnomAD3 exomes AF: 0.0491 AC: 8460 AN: 172224 Hom.: 226 AF XY: 0.0483 AC XY: 2783 AN XY: 57616

Gnomad AFR exome AF: 0.0103

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0571

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0172

Gnomad FIN exome AF: 0.0559

Gnomad NFE exome AF: 0.0773

Gnomad OTH exome AF: 0.0540

GnomAD4 exome AF: 0.0729 AC: 79646 AN: 1092138 Hom.: 2376 Cov.: 30 AF XY: 0.0698 AC XY: 24994 AN XY: 357868

Gnomad4 AFR exome AF: 0.00801

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.0524

Gnomad4 EAS exome AF: 0.0000333

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.0604

Gnomad4 NFE exome AF: 0.0851

Gnomad4 OTH exome AF: 0.0586

GnomAD4 genome AF: 0.0492 AC: 5493 AN: 111703 Hom.: 153 Cov.: 23 AF XY: 0.0438 AC XY: 1485 AN XY: 33895

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0413

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.0115

Gnomad4 FIN AF: 0.0572

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0401

Alfa AF: 0.0719 Hom.: 3955

Bravo AF: 0.0455

TwinsUK AF: 0.0917 AC: 340

ALSPAC AF: 0.0886 AC: 256

ESP6500AA AF: 0.0117 AC: 45

ESP6500EA AF: 0.0789 AC: 531

ExAC AF: 0.0480 AC: 5825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.72
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	.;.;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D;D
MetaRNN	Benign	0.0083	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.41	N;N;N
REVEL	Benign	0.095
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.67	T;T;T
Polyphen		0.94	.;.;P
Vest4		0.29
MPC		0.12
ClinPred		0.021	T
GERP RS		5.2
Varity_R		0.31
gMVP		0.44

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: rs35318931; hg19: chrX-38009121; COSMIC: COSV59438791;