6-25812862-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005074.5(SLC17A1):​c.866T>C​(p.Ile289Thr) variant causes a missense 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC17A1
NM_005074.5 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24

Publications

0 publications found
Variant links:
Genes affected
SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC17A1NM_005074.5 linkc.866T>C p.Ile289Thr missense_variant Exon 8 of 13 ENST00000244527.10 NP_005065.2 Q14916-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC17A1ENST00000244527.10 linkc.866T>C p.Ile289Thr missense_variant Exon 8 of 13 5 NM_005074.5 ENSP00000244527.4 Q14916-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.866T>C (p.I289T) alteration is located in exon 8 (coding exon 7) of the SLC17A1 gene. This alteration results from a T to C substitution at nucleotide position 866, causing the isoleucine (I) at amino acid position 289 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Uncertain
0.099
D
BayesDel_noAF
Benign
-0.090
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;T
Eigen
Benign
0.12
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.76
.;T
M_CAP
Benign
0.029
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.9
M;M
PhyloP100
4.2
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.77
MutPred
0.67
Loss of stability (P = 0.064);Loss of stability (P = 0.064);
MVP
0.77
MPC
0.51
ClinPred
0.98
D
GERP RS
3.7
Varity_R
0.79
gMVP
0.53
Mutation Taster
=95/5
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

hg19: chr6-25813090; API