X-38160997-G-C

Variant names:

• chrX-38160997-G-C
• rs374069621
• NM_006307.5:c.711C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006307.5(SRPX):​c.711C>G​(p.Ile237Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000885 in 1,208,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000095 (0 hom. 43 hem.)
• Consequence: SRPX NM_006307.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24905866).
• BS2: High Hemizygotes in GnomAdExome4 at 43 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.711C>G	p.Ile237Met	missense	Exon 6 of 10	NP_006298.1	P78539-1
	SRPX	NM_001170750.2		c.651C>G	p.Ile217Met	missense	Exon 5 of 9	NP_001164221.1	P78539-5
	SRPX	NM_001170751.2		c.534C>G	p.Ile178Met	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.711C>G	p.Ile237Met	missense	Exon 6 of 10	ENSP00000367794.3	P78539-1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-505124G>C		intron	N/A	ENSP00000417050.1	B4E171
	SRPX	ENST00000898757.1		c.711C>G	p.Ile237Met	missense	Exon 6 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes AF: 0.0000270 AC: 3 AN: 111306 Hom.: 0 Cov.: 22

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: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000218 AC: 4 AN: 183308 AF XY: 0.0000443

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: 0.0000489

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000948 AC: 104 AN: 1097428 Hom.: 0 Cov.: 29 AF XY: 0.000119 AC XY: 43 AN XY: 362820

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19372

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4023

European-Non Finnish (NFE) AF: 0.000122 AC: 103 AN: 841652

Other (OTH) AF: 0.0000217 AC: 1 AN: 46055

GnomAD4 genome AF: 0.0000270 AC: 3 AN: 111306 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33512

African (AFR) AF: 0.00 AC: 0 AN: 30533

American (AMR) AF: 0.00 AC: 0 AN: 10426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.00 AC: 0 AN: 2580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53093

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.0000494 AC: 6

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	Benign	0.24
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.3
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.51	P
Vest4		0.29
MVP		0.61
MPC		0.16
ClinPred		0.40	T
GERP RS		2.1
Varity_R		0.59
gMVP		0.65
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs374069621; hg19: chrX-38020250;