rs1165196

Variant names:

• chr6-25812922-G-A
• rs1165196
• NM_005074.5:c.806C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-25812922-G-A
• chr6-25812922-G-C
• chr6-25812922-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005074.5(SLC17A1):​c.806C>T​(p.Thr269Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,612,780 control chromosomes in the GnomAD database, including 285,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T269A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.66 (35073 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250912 hom.)
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 114 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.819695E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A1	NM_005074.5	c.806C>T	p.Thr269Ile	missense_variant	Exon 8 of 13	ENST00000244527.10	NP_005065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A1	ENST00000244527.10	c.806C>T	p.Thr269Ile	missense_variant	Exon 8 of 13	5	NM_005074.5	ENSP00000244527.4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100595 AN: 152074 Hom.: 35012 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.660

GnomAD2 exomes AF: 0.618 AC: 155166 AN: 251110 AF XY: 0.601

Gnomad AFR exome AF: 0.879

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.863

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.580

GnomAD4 exome AF: 0.581 AC: 847989 AN: 1460588 Hom.: 250912 Cov.: 36 AF XY: 0.576 AC XY: 418689 AN XY: 726668

African (AFR) AF: 0.890 AC: 29797 AN: 33464

American (AMR) AF: 0.713 AC: 31886 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 12565 AN: 26122

East Asian (EAS) AF: 0.846 AC: 33571 AN: 39690

South Asian (SAS) AF: 0.529 AC: 45623 AN: 86190

European-Finnish (FIN) AF: 0.626 AC: 33439 AN: 53408

Middle Eastern (MID) AF: 0.575 AC: 3314 AN: 5764

European-Non Finnish (NFE) AF: 0.560 AC: 621816 AN: 1110896

Other (OTH) AF: 0.596 AC: 35978 AN: 60356

GnomAD4 genome AF: 0.662 AC: 100717 AN: 152192 Hom.: 35073 Cov.: 32 AF XY: 0.663 AC XY: 49351 AN XY: 74400

African (AFR) AF: 0.873 AC: 36285 AN: 41546

American (AMR) AF: 0.655 AC: 10010 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4314 AN: 5188

South Asian (SAS) AF: 0.530 AC: 2557 AN: 4822

European-Finnish (FIN) AF: 0.643 AC: 6807 AN: 10580

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37282 AN: 67988

Other (OTH) AF: 0.661 AC: 1394 AN: 2110

Alfa AF: 0.585 Hom.: 126379

Bravo AF: 0.678

TwinsUK AF: 0.558 AC: 2070

ALSPAC AF: 0.555 AC: 2138

ESP6500AA AF: 0.861 AC: 3795

ESP6500EA AF: 0.546 AC: 4698

ExAC AF: 0.616 AC: 74777

Asia WGS AF: 0.681 AC: 2369 AN: 3478

EpiCase AF: 0.541

EpiControl AF: 0.532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.5
DANN	Benign	0.32
DEOGEN2	Benign	0.050	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.000080	N
LIST_S2	Benign	0.14	.;T
MetaRNN	Benign	0.0000018	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.94	N;N
PhyloP100		2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.9	N;N
REVEL	Benign	0.11
Sift	Benign	0.37	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0	B;B
Vest4		0.029
MPC		0.10
ClinPred		0.0078	T
GERP RS		3.7
Varity_R		0.031
gMVP		0.071
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1165196; hg19: chr6-25813150; COSMIC: COSV107301914;