chr15-48134888-C-G
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_205850.3(SLC24A5):c.494C>G(p.Ser165Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SLC24A5
NM_205850.3 stop_gained
NM_205850.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 6.42
Genes affected
SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-48134888-C-G is Pathogenic according to our data. Variant chr15-48134888-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 2431038.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC24A5 | NM_205850.3 | c.494C>G | p.Ser165Ter | stop_gained | 5/9 | ENST00000341459.8 | |
MYEF2 | NM_016132.5 | c.*8020G>C | 3_prime_UTR_variant | 17/17 | ENST00000324324.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A5 | ENST00000341459.8 | c.494C>G | p.Ser165Ter | stop_gained | 5/9 | 1 | NM_205850.3 | P1 | |
SLC24A5 | ENST00000449382.2 | c.314C>G | p.Ser105Ter | stop_gained | 4/8 | 1 | |||
MYEF2 | ENST00000324324.12 | c.*8020G>C | 3_prime_UTR_variant | 17/17 | 1 | NM_016132.5 | P4 | ||
SLC24A5 | ENST00000463289.1 | n.254C>G | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Oculocutaneous albinism type 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Pediatrics Genetics, Post Graduate Institute of Medical Education and Research | Mar 01, 2023 | PVS1: null variant (nonsense, frameshift, canonical +- 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
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.