chrX-38160935-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006307.5(SRPX):c.773G>T(p.Arg258Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Consequence
SRPX
NM_006307.5 missense, splice_region
NM_006307.5 missense, splice_region
Scores
1
8
8
Splicing: ADA: 0.05387
2
Clinical Significance
Conservation
PhyloP100: 2.65
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRPX | NM_006307.5 | c.773G>T | p.Arg258Ile | missense_variant, splice_region_variant | 6/10 | ENST00000378533.4 | NP_006298.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRPX | ENST00000378533.4 | c.773G>T | p.Arg258Ile | missense_variant, splice_region_variant | 6/10 | 1 | NM_006307.5 | ENSP00000367794 | P2 | |
SRPX | ENST00000544439.5 | c.713G>T | p.Arg238Ile | missense_variant, splice_region_variant | 5/9 | 2 | ENSP00000440758 | A2 | ||
SRPX | ENST00000432886.6 | c.596G>T | p.Arg199Ile | missense_variant, splice_region_variant | 5/9 | 2 | ENSP00000411165 | |||
SRPX | ENST00000538295.5 | c.773G>T | p.Arg258Ile | missense_variant, splice_region_variant | 6/9 | 2 | ENSP00000445034 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.773G>T (p.R258I) alteration is located in exon 6 (coding exon 6) of the SRPX gene. This alteration results from a G to T substitution at nucleotide position 773, causing the arginine (R) at amino acid position 258 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.98
.;.;.;D
Vest4
MutPred
0.54
.;.;Gain of methylation at K260 (P = 0.0365);Gain of methylation at K260 (P = 0.0365);
MVP
MPC
0.084
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.