chr6-25819070-A-G

Variant names:

• chr6-25819070-A-G
• rs776287891
• NM_005074.5:c.614T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005074.5(SLC17A1):​c.614T>C​(p.Phe205Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,590,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SLC17A1 NM_005074.5 missense, splice_region
• Scores: Splicing: ADA: 0.009837
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A1	NM_005074.5	c.614T>C	p.Phe205Ser	missense_variant, splice_region_variant	Exon 6 of 13	ENST00000244527.10	NP_005065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A1	ENST00000244527.10	c.614T>C	p.Phe205Ser	missense_variant, splice_region_variant	Exon 6 of 13	5	NM_005074.5	ENSP00000244527.4
SLC17A1	ENST00000468082.1	c.614T>C	p.Phe205Ser	missense_variant, splice_region_variant	Exon 5 of 10	1		ENSP00000420546.1
SLC17A1	ENST00000476801.5	c.614T>C	p.Phe205Ser	missense_variant, splice_region_variant	Exon 6 of 12	2		ENSP00000420614.1
SLC17A1	ENST00000377886.6	n.614T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 12	5		ENSP00000367118.2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000864 AC: 2 AN: 231414 AF XY: 0.00

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1437860 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714884

African (AFR) AF: 0.000156 AC: 5 AN: 31978

American (AMR) AF: 0.00 AC: 0 AN: 38728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.00 AC: 0 AN: 80450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104438

Other (OTH) AF: 0.00 AC: 0 AN: 59238

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74374

African (AFR) AF: 0.000121 AC: 5 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.614T>C (p.F205S) alteration is located in exon 6 (coding exon 5) of the SLC17A1 gene. This alteration results from a T to C substitution at nucleotide position 614, causing the phenylalanine (F) at amino acid position 205 to be replaced by a serine (S). 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	0.35
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.65	.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;M;M
PhyloP100		2.0
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-7.2	D;D;D
REVEL	Benign	0.27
Sift	Benign	0.035	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.83	P;P;P
Vest4		0.78
MutPred		0.61		Gain of glycosylation at F205 (P = 0.0052);Gain of glycosylation at F205 (P = 0.0052);Gain of glycosylation at F205 (P = 0.0052);
MVP		0.68
MPC		0.64
ClinPred		0.75	D
GERP RS		1.9
Varity_R		0.60
gMVP		0.56
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0098
dbscSNV1_RF	Benign	0.17
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

Other links and lift over

dbSNP: rs776287891; hg19: chr6-25819298;