chr15-48134912-TCAGAGACTGTG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_205850.3(SLC24A5):c.522_532del(p.Arg174SerfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
SLC24A5
NM_205850.3 frameshift
NM_205850.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.27
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 15-48134912-TCAGAGACTGTG-T is Pathogenic according to our data. Variant chr15-48134912-TCAGAGACTGTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 1939262.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.522_532del | p.Arg174SerfsTer5 | frameshift_variant | 5/9 | ENST00000341459.8 | |
MYEF2 | NM_016132.5 | c.*7985_*7995del | 3_prime_UTR_variant | 17/17 | ENST00000324324.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A5 | ENST00000341459.8 | c.522_532del | p.Arg174SerfsTer5 | frameshift_variant | 5/9 | 1 | NM_205850.3 | P1 | |
SLC24A5 | ENST00000449382.2 | c.342_352del | p.Arg114SerfsTer5 | frameshift_variant | 4/8 | 1 | |||
MYEF2 | ENST00000324324.12 | c.*7985_*7995del | 3_prime_UTR_variant | 17/17 | 1 | NM_016132.5 | P4 | ||
SLC24A5 | ENST00000463289.1 | n.282_292del | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460074Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 726188
GnomAD4 exome
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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
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 02, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SLC24A5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg174Serfs*5) in the SLC24A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC24A5 are known to be pathogenic (PMID: 23985994, 26686029). - |
Computational scores
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Name
Calibrated prediction
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.