rs1426654
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_205850.3(SLC24A5):c.331A>G(p.Thr111Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,472 control chromosomes in the GnomAD database, including 59,639 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 17328 hom., cov: 32)
Exomes 𝑓: 0.081 ( 42311 hom. )
Consequence
SLC24A5
NM_205850.3 missense
NM_205850.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 7.57
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=1.1562395E-6).
BP6
?
Variant 15-48134287-A-G is Benign according to our data. Variant chr15-48134287-A-G is described in ClinVar as [Benign]. Clinvar id is 263273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC24A5 | NM_205850.3 | c.331A>G | p.Thr111Ala | missense_variant | 3/9 | ENST00000341459.8 | |
SLC24A5 | XM_047432394.1 | c.331A>G | p.Thr111Ala | missense_variant | 3/8 | ||
SLC24A5 | XM_024449901.2 | c.-9A>G | 5_prime_UTR_variant | 2/8 | |||
SLC24A5 | XM_047432395.1 | c.-9A>G | 5_prime_UTR_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A5 | ENST00000341459.8 | c.331A>G | p.Thr111Ala | missense_variant | 3/9 | 1 | NM_205850.3 | P1 | |
SLC24A5 | ENST00000449382.2 | c.151A>G | p.Thr51Ala | missense_variant | 2/8 | 1 | |||
SLC24A5 | ENST00000463289.1 | n.91A>G | non_coding_transcript_exon_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.298 AC: 45263AN: 152008Hom.: 17249 Cov.: 32
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GnomAD3 exomes AF: 0.230 AC: 57776AN: 251246Hom.: 21227 AF XY: 0.196 AC XY: 26657AN XY: 135786
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GnomAD4 exome AF: 0.0806 AC: 117787AN: 1461346Hom.: 42311 Cov.: 31 AF XY: 0.0786 AC XY: 57143AN XY: 726986
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GnomAD4 genome ? AF: 0.299 AC: 45411AN: 152126Hom.: 17328 Cov.: 32 AF XY: 0.301 AC XY: 22390AN XY: 74392
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27720
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2020 | This variant is associated with the following publications: (PMID: 17999355, 18650849, 24244186, 23071798, 16357253, 29025994, 31315583) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
P;P
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at