chrX-38149868-G-A

Variant names:

• chrX-38149868-G-A
• rs35318931
• NM_006307.5:c.1238C>T

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SRPX	NM_006307.5	c.1238C>T	p.Ser413Phe	missense_variant	Exon 10 of 10	ENST00000378533.4	NP_006298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4	c.1238C>T	p.Ser413Phe	missense_variant	Exon 10 of 10	1	NM_006307.5	ENSP00000367794.3
ENSG00000250349	ENST00000465127.1	c.172-516253G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 5491 AN: 111652 Hom.: 153 Cov.: 23

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

GnomAD2 exomes AF: 0.0491 AC: 8460 AN: 172224 AF XY: 0.0483

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 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 AC: 210 AN: 26209

Gnomad4 AMR exome AF: 0.0236 AC: 807 AN: 34196

Gnomad4 ASJ exome AF: 0.0524 AC: 1003 AN: 19149

Gnomad4 EAS exome AF: 0.0000333 AC: 1 AN: 30036

Gnomad4 SAS exome AF: 0.0189 AC: 988 AN: 52334

Gnomad4 FIN exome AF: 0.0604 AC: 2438 AN: 40376

Gnomad4 NFE exome AF: 0.0851 AC: 71488 AN: 839903

Gnomad4 Remaining exome AF: 0.0586 AC: 2686 AN: 45859

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 AC: 0.0114083 AN: 0.0114083

Gnomad4 AMR AF: 0.0318 AC: 0.0317821 AN: 0.0317821

Gnomad4 ASJ AF: 0.0413 AC: 0.0412566 AN: 0.0412566

Gnomad4 EAS AF: 0.000281 AC: 0.000281452 AN: 0.000281452

Gnomad4 SAS AF: 0.0115 AC: 0.0114811 AN: 0.0114811

Gnomad4 FIN AF: 0.0572 AC: 0.0572279 AN: 0.0572279

Gnomad4 NFE AF: 0.0796 AC: 0.0796467 AN: 0.0796467

Gnomad4 OTH AF: 0.0401 AC: 0.0401316 AN: 0.0401316

Alfa AF: 0.0692 Hom.: 4553

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
Mutation Taster		=98/2	polymorphism (auto)

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;