chr15-84905547-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004213.5(SLC28A1):c.612G>C(p.Trp204Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
SLC28A1
NM_004213.5 missense
NM_004213.5 missense
Scores
7
7
4
Clinical Significance
Conservation
PhyloP100: 7.32
Genes affected
SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.926
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC28A1 | NM_004213.5 | c.612G>C | p.Trp204Cys | missense_variant | 8/19 | ENST00000394573.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC28A1 | ENST00000394573.6 | c.612G>C | p.Trp204Cys | missense_variant | 8/19 | 1 | NM_004213.5 | P1 | |
SLC28A1 | ENST00000286749.3 | c.612G>C | p.Trp204Cys | missense_variant | 7/18 | 1 | P1 | ||
SLC28A1 | ENST00000538177.5 | c.612G>C | p.Trp204Cys | missense_variant | 7/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251438Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
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GnomAD4 exome AF: 0.0000281 AC: 41AN: 1459838Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726400
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74360
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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 07, 2022 | The c.612G>C (p.W204C) alteration is located in exon 8 (coding exon 6) of the SLC28A1 gene. This alteration results from a G to C substitution at nucleotide position 612, causing the tryptophan (W) at amino acid position 204 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0773);Loss of MoRF binding (P = 0.0773);Loss of MoRF binding (P = 0.0773);
MVP
MPC
0.55
ClinPred
D
GERP RS
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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