12-108623244-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000550948.2(SELPLG):c.1064G>A(p.Arg355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,610,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000550948.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SELPLG | NM_003006.4 | c.1064G>A | p.Arg355His | missense_variant | 2/2 | ENST00000550948.2 | NP_002997.2 | |
SELPLG | NM_001206609.2 | c.1112G>A | p.Arg371His | missense_variant | 2/2 | NP_001193538.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SELPLG | ENST00000550948.2 | c.1064G>A | p.Arg355His | missense_variant | 2/2 | 1 | NM_003006.4 | ENSP00000447752 | P2 | |
SELPLG | ENST00000228463.6 | c.1112G>A | p.Arg371His | missense_variant | 2/2 | 2 | ENSP00000228463 | A2 | ||
SELPLG | ENST00000388962.4 | c.1034G>A | p.Arg345His | missense_variant | 2/2 | 5 | ENSP00000373614 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000139 AC: 21AN: 150672Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000108 AC: 27AN: 250848Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135556
GnomAD4 exome AF: 0.000171 AC: 250AN: 1459766Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 117AN XY: 726210
GnomAD4 genome AF: 0.000139 AC: 21AN: 150672Hom.: 0 Cov.: 33 AF XY: 0.000150 AC XY: 11AN XY: 73550
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The c.1064G>A (p.R355H) alteration is located in exon 2 (coding exon 1) of the SELPLG gene. This alteration results from a G to A substitution at nucleotide position 1064, causing the arginine (R) at amino acid position 355 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at