6-25914573-G-A

Variant names:

• chr6-25914573-G-A
• rs2071299
• NM_001286123.3:c.1302+7C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001286123.3(SLC17A2):​c.1302+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,580,674 control chromosomes in the GnomAD database, including 127,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (10394 hom., cov: 31)
  • Exomes 𝑓: 0.40 (116956 hom.)
• Consequence: SLC17A2 NM_001286123.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 26 publications found

Genes affected

SLC17A2 (HGNC:10930): (solute carrier family 17 member 2) Predicted to enable sialic acid transmembrane transporter activity. Predicted to be involved in sialic acid transport. Predicted to be located in membrane. Predicted to be active in lysosome. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286123.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A2	NM_001286123.3	MANE Select	c.1302+7C>T		splice_region intron	N/A	NP_001273052.1	O00624-3
	SLC17A2	NM_001286125.2		c.1161C>T	p.Gly387Gly	synonymous	Exon 9 of 10	NP_001273054.1
	SLC17A2	NM_005835.4		c.1154+7C>T		splice_region intron	N/A	NP_005826.1	O00624-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A2	ENST00000377850.8	TSL:5 MANE Select	c.1302+7C>T		splice_region intron	N/A	ENSP00000367081.3	O00624-3
	SLC17A2	ENST00000360488.7	TSL:1	c.1154+7C>T		splice_region intron	N/A	ENSP00000353677.3	O00624-2
	SLC17A2	ENST00000265425.3	TSL:5	c.1309C>T	p.Pro437Ser	missense	Exon 10 of 11	ENSP00000265425.3	O00624-1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53030 AN: 151776 Hom.: 10388 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.416 AC: 104115 AN: 250374 AF XY: 0.413

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.709

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.397 AC: 566615 AN: 1428778 Hom.: 116956 Cov.: 27 AF XY: 0.397 AC XY: 283129 AN XY: 712606

African (AFR) AF: 0.171 AC: 5653 AN: 33070

American (AMR) AF: 0.480 AC: 21429 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9748 AN: 25918

East Asian (EAS) AF: 0.702 AC: 27720 AN: 39474

South Asian (SAS) AF: 0.403 AC: 34420 AN: 85506

European-Finnish (FIN) AF: 0.414 AC: 22084 AN: 53352

Middle Eastern (MID) AF: 0.319 AC: 1817 AN: 5692

European-Non Finnish (NFE) AF: 0.388 AC: 419879 AN: 1081828

Other (OTH) AF: 0.402 AC: 23865 AN: 59340

GnomAD4 genome AF: 0.349 AC: 53051 AN: 151896 Hom.: 10394 Cov.: 31 AF XY: 0.355 AC XY: 26370 AN XY: 74262

African (AFR) AF: 0.180 AC: 7467 AN: 41426

American (AMR) AF: 0.412 AC: 6282 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3582 AN: 5140

South Asian (SAS) AF: 0.417 AC: 2014 AN: 4826

European-Finnish (FIN) AF: 0.420 AC: 4430 AN: 10548

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26749 AN: 67920

Other (OTH) AF: 0.372 AC: 784 AN: 2110

Alfa AF: 0.370 Hom.: 20802

Bravo AF: 0.344

TwinsUK AF: 0.377 AC: 1397

ALSPAC AF: 0.376 AC: 1451

ESP6500AA AF: 0.186 AC: 818

ESP6500EA AF: 0.390 AC: 3352

ExAC AF: 0.407 AC: 49364

Asia WGS AF: 0.528 AC: 1836 AN: 3478

EpiCase AF: 0.388

EpiControl AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0000051	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.044
Sift	Benign	0.53	T
Sift4G	Pathogenic	0.0	D
Vest4		0.017
ClinPred		0.0035	T
GERP RS		1.7
Varity_R		0.031
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: 2

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

Other links and lift over

dbSNP: rs2071299; hg19: chr6-25914801; COSMIC: COSV55353104;