chrX-38154558-C-T

Variant names:

• chrX-38154558-C-T
• rs144518030
• NM_006307.5:c.1115G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_006307.5(SRPX):​c.1115G>A​(p.Arg372Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,206,728 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R372L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000016 (0 hom. 6 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

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.1115G>A	p.Arg372Gln	missense	Exon 9 of 10	NP_006298.1	P78539-1
	SRPX	NM_001170750.2		c.1055G>A	p.Arg352Gln	missense	Exon 8 of 9	NP_001164221.1	P78539-5
	SRPX	NM_001170751.2		c.938G>A	p.Arg313Gln	missense	Exon 8 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.1115G>A	p.Arg372Gln	missense	Exon 9 of 10	ENSP00000367794.3	P78539-1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-511563C>T		intron	N/A	ENSP00000417050.1	B4E171
	SRPX	ENST00000898757.1		c.1187G>A	p.Arg396Gln	missense	Exon 10 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111517 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.000663

GnomAD2 exomes AF: 0.0000114 AC: 2 AN: 174903 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000258

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 18 AN: 1095161 Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 6 AN XY: 360855

African (AFR) AF: 0.00 AC: 0 AN: 26350

American (AMR) AF: 0.00 AC: 0 AN: 34904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 30112

South Asian (SAS) AF: 0.00 AC: 0 AN: 53333

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4111

European-Non Finnish (NFE) AF: 0.0000214 AC: 18 AN: 840703

Other (OTH) AF: 0.00 AC: 0 AN: 45988

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111567 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33773

African (AFR) AF: 0.00 AC: 0 AN: 30711

American (AMR) AF: 0.00 AC: 0 AN: 10545

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.00 AC: 0 AN: 2613

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53079

Other (OTH) AF: 0.000655 AC: 1 AN: 1527

Alfa AF: 0.00 Hom.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.73		Loss of stability (P = 0.1378)
MVP		0.96
MPC		0.16
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.98
gMVP		0.85
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs144518030; hg19: chrX-38013811;