X-38160972-C-T

Variant names:

• chrX-38160972-C-T
• rs752895004
• NM_006307.5:c.736G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006307.5(SRPX):​c.736G>A​(p.Glu246Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,525 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E246Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• Publications: 0 publications found

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: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006307.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX	NM_006307.5	MANE Select	c.736G>A	p.Glu246Lys	missense	Exon 6 of 10	NP_006298.1	P78539-1
	SRPX	NM_001170750.2		c.676G>A	p.Glu226Lys	missense	Exon 5 of 9	NP_001164221.1	P78539-5
	SRPX	NM_001170751.2		c.559G>A	p.Glu187Lys	missense	Exon 5 of 9	NP_001164222.1	P78539-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX	ENST00000378533.4	TSL:1 MANE Select	c.736G>A	p.Glu246Lys	missense	Exon 6 of 10	ENSP00000367794.3	P78539-1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-505149C>T		intron	N/A	ENSP00000417050.1	B4E171
	SRPX	ENST00000898757.1		c.736G>A	p.Glu246Lys	missense	Exon 6 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096525 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1 AN XY: 361973

African (AFR) AF: 0.00 AC: 0 AN: 26385

American (AMR) AF: 0.00 AC: 0 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19339

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 53707

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40457

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4066

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841163

Other (OTH) AF: 0.00 AC: 0 AN: 46017

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	1.0	T
Polyphen		0.95	P
Vest4		0.59
MutPred		0.60		Gain of MoRF binding (P = 0.0112)
MVP		0.69
MPC		0.12
ClinPred		0.76	D
GERP RS		5.0
Varity_R		0.54
gMVP		0.61
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs752895004; hg19: chrX-38020225;