rs144518030

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-38154558-C-A
• chrX-38154558-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_006307.5(SRPX):​c.1115G>T​(p.Arg372Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 1,206,728 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 297 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.00085 (0 hom. 287 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779
• BS2: High Hemizygotes in GnomAd4 at 10 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>T	p.Arg372Leu	missense	Exon 9 of 10	NP_006298.1	P78539-1
	SRPX	NM_001170750.2		c.1055G>T	p.Arg352Leu	missense	Exon 8 of 9	NP_001164221.1	P78539-5
	SRPX	NM_001170751.2		c.938G>T	p.Arg313Leu	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>T	p.Arg372Leu	missense	Exon 9 of 10	ENSP00000367794.3	P78539-1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-511563C>A		intron	N/A	ENSP00000417050.1	B4E171
	SRPX	ENST00000898757.1		c.1187G>T	p.Arg396Leu	missense	Exon 10 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes AF: 0.000475 AC: 53 AN: 111517 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000285

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: 0.000810

Gnomad OTH AF: 0.000663

GnomAD2 exomes AF: 0.000314 AC: 55 AN: 174903 AF XY: 0.000299

Gnomad AFR exome AF: 0.0000800

Gnomad AMR exome AF: 0.0000748

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000647

Gnomad NFE exome AF: 0.000645

Gnomad OTH exome AF: 0.000229

GnomAD4 exome AF: 0.000852 AC: 933 AN: 1095161 Hom.: 0 Cov.: 30 AF XY: 0.000795 AC XY: 287 AN XY: 360855

African (AFR) AF: 0.0000380 AC: 1 AN: 26350

American (AMR) AF: 0.0000860 AC: 3 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: 0.00108 AC: 909 AN: 840703

Other (OTH) AF: 0.000435 AC: 20 AN: 45988

GnomAD4 genome AF: 0.000475 AC: 53 AN: 111567 Hom.: 0 Cov.: 23 AF XY: 0.000296 AC XY: 10 AN XY: 33773

African (AFR) AF: 0.000195 AC: 6 AN: 30711

American (AMR) AF: 0.000284 AC: 3 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: 0.000810 AC: 43 AN: 53079

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

Alfa AF: 0.000710 Hom.: 33

Bravo AF: 0.000465

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.000280 AC: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MVP		0.97
MPC		0.16
ClinPred		0.36	T
GERP RS		5.6
Varity_R		0.94
gMVP		0.88
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;