6-25811658-C-T

Variant names:

• chr6-25811658-C-T
• rs200727863
• NM_005074.5:c.1010G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005074.5(SLC17A1):​c.1010G>A​(p.Arg337Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,830 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R337W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A1	NM_005074.5	c.1010G>A	p.Arg337Gln	missense_variant	Exon 9 of 13	ENST00000244527.10	NP_005065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A1	ENST00000244527.10	c.1010G>A	p.Arg337Gln	missense_variant	Exon 9 of 13	5	NM_005074.5	ENSP00000244527.4

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000207 AC: 52 AN: 251128 AF XY: 0.000243

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000120 AC: 176 AN: 1461654 Hom.: 1 Cov.: 32 AF XY: 0.000142 AC XY: 103 AN XY: 727134

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000579 AC: 23 AN: 39698

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53406

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.0000980 AC: 109 AN: 1111848

Other (OTH) AF: 0.000166 AC: 10 AN: 60380

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74390

African (AFR) AF: 0.0000723 AC: 3 AN: 41522

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000234 Hom.: 0

Bravo AF: 0.000147

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000206 AC: 25

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1010G>A (p.R337Q) alteration is located in exon 9 (coding exon 8) of the SLC17A1 gene. This alteration results from a G to A substitution at nucleotide position 1010, causing the arginine (R) at amino acid position 337 to be replaced by a glutamine (Q). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.70	D;D;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Uncertain	-0.0073	T
MutationAssessor	Pathogenic	3.6	H;H;.
PhyloP100		4.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.86
MVP		0.69
MPC		0.53
ClinPred		0.70	D
GERP RS		3.5
Varity_R		0.88
gMVP		0.84
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200727863; hg19: chr6-25811886; COSMIC: COSV55079844;