6-25813202-A-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005074.5(SLC17A1):​c.628T>C​(p.Cys210Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,634 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC17A1
NM_005074.5 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.961

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC17A1NM_005074.5 linkc.628T>C p.Cys210Arg missense_variant Exon 7 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.628T>C p.Cys210Arg missense_variant Exon 7 of 13 5 NM_005074.5 ENSP00000244527.4 Q14916-1
SLC17A1ENST00000468082.1 linkc.628T>C p.Cys210Arg missense_variant Exon 6 of 10 1 ENSP00000420546.1 Q14916-2
SLC17A1ENST00000476801.5 linkc.628T>C p.Cys210Arg missense_variant Exon 7 of 12 2 ENSP00000420614.1 Q14916-1
SLC17A1ENST00000377886.6 linkn.617-210T>C intron_variant Intron 6 of 11 5 ENSP00000367118.2 E9PGW3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461634
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727166
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111776
Other (OTH)
AF:
0.00
AC:
0
AN:
60388
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
Dec 24, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.628T>C (p.C210R) alteration is located in exon 7 (coding exon 6) of the SLC17A1 gene. This alteration results from a T to C substitution at nucleotide position 628, causing the cysteine (C) at amino acid position 210 to be replaced by an arginine (R). 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
0.94
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;D;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.87
.;D;D
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Benign
-0.50
T
MutationAssessor
Pathogenic
3.1
M;M;M
PhyloP100
3.3
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-11
D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.80
MutPred
0.81
Gain of methylation at C210 (P = 0.0026);Gain of methylation at C210 (P = 0.0026);Gain of methylation at C210 (P = 0.0026);
MVP
0.86
MPC
0.66
ClinPred
1.0
D
GERP RS
3.3
Varity_R
0.98
gMVP
0.70
Mutation Taster
=84/16
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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

dbSNP: rs754443994; hg19: chr6-25813430; API