rs6820230

Variant names:

• chr4-10025918-C-T
• rs6820230
• ENST00000309065.7:c.49G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000309065.7(SLC2A9):​c.49G>A​(p.Ala17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,611,940 control chromosomes in the GnomAD database, including 63,022 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8994 hom., cov: 32)
  • Exomes 𝑓: 0.26 (54028 hom.)
• Consequence: SLC2A9 ENST00000309065.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.136
• Publications: 45 publications found

Genes affected

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SLC2A9-AS1 (HGNC:40636): (SLC2A9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7085671E-4).
• BP6: Variant 4-10025918-C-T is Benign according to our data. Variant chr4-10025918-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_001001290.2	c.49G>A	p.Ala17Thr	missense_variant	Exon 2 of 13		NP_001001290.1
SLC2A9	XM_011513858.2	c.49G>A	p.Ala17Thr	missense_variant	Exon 2 of 14		XP_011512160.1
SLC2A9	XM_047415973.1	c.49G>A	p.Ala17Thr	missense_variant	Exon 2 of 14		XP_047271929.1
SLC2A9	XM_047415975.1	c.49G>A	p.Ala17Thr	missense_variant	Exon 2 of 13		XP_047271931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000309065.7	c.49G>A	p.Ala17Thr	missense_variant	Exon 2 of 13	1		ENSP00000311383.3
SLC2A9	ENST00000505104.5	n.170G>A		non_coding_transcript_exon_variant	Exon 2 of 12	1
SLC2A9	ENST00000506583.5	c.49G>A	p.Ala17Thr	missense_variant	Exon 3 of 14	5		ENSP00000422209.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48603 AN: 151856 Hom.: 8983 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.235 AC: 58989 AN: 250740 AF XY: 0.228

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.0921

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.262 AC: 382152 AN: 1459970 Hom.: 54028 Cov.: 34 AF XY: 0.256 AC XY: 186229 AN XY: 726216

African (AFR) AF: 0.511 AC: 17075 AN: 33424

American (AMR) AF: 0.156 AC: 6988 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5352 AN: 26086

East Asian (EAS) AF: 0.0717 AC: 2845 AN: 39688

South Asian (SAS) AF: 0.0978 AC: 8400 AN: 85930

European-Finnish (FIN) AF: 0.275 AC: 14678 AN: 53394

Middle Eastern (MID) AF: 0.214 AC: 1232 AN: 5766

European-Non Finnish (NFE) AF: 0.279 AC: 309662 AN: 1110660

Other (OTH) AF: 0.264 AC: 15920 AN: 60326

GnomAD4 genome AF: 0.320 AC: 48630 AN: 151970 Hom.: 8994 Cov.: 32 AF XY: 0.313 AC XY: 23266 AN XY: 74284

African (AFR) AF: 0.502 AC: 20799 AN: 41462

American (AMR) AF: 0.223 AC: 3407 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3464

East Asian (EAS) AF: 0.0924 AC: 478 AN: 5174

South Asian (SAS) AF: 0.0912 AC: 440 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2898 AN: 10524

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19025 AN: 67938

Other (OTH) AF: 0.302 AC: 636 AN: 2104

Alfa AF: 0.284 Hom.: 25753

Bravo AF: 0.326

TwinsUK AF: 0.279 AC: 1035

ALSPAC AF: 0.288 AC: 1110

ESP6500AA AF: 0.493 AC: 2173

ESP6500EA AF: 0.272 AC: 2340

ExAC AF: 0.243 AC: 29481

Asia WGS AF: 0.125 AC: 441 AN: 3478

EpiCase AF: 0.269

EpiControl AF: 0.278

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.1
DANN	Benign	0.53
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.39	.;T;T
MetaRNN	Benign	0.00017	T;T;T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.14
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.58	T;T;T
Sift4G	Benign	0.71	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.018
ClinPred		0.0030	T
GERP RS		0.89
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6820230; hg19: chr4-10027542; COSMIC: COSV53318828; COSMIC: COSV53318828;