rs6820230

chr4-10025918-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 11/13 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, single submitter B:1
• Conservation: PhyloP100: -0.136

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1266845.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
SLC2A9	NM_001001290.2	c.49G>A	p.Ala17Thr	missense_variant	2/13
SLC2A9	XM_011513858.2	c.49G>A	p.Ala17Thr	missense_variant	2/14
SLC2A9	XM_047415973.1	c.49G>A	p.Ala17Thr	missense_variant	2/14
SLC2A9	XM_047415975.1	c.49G>A	p.Ala17Thr	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A9	ENST00000309065.7	c.49G>A	p.Ala17Thr	missense_variant	2/13	1		P2
SLC2A9	ENST00000505104.5	n.170G>A		non_coding_transcript_exon_variant	2/12	1
SLC2A9	ENST00000506583.5	c.49G>A	p.Ala17Thr	missense_variant	3/14	5		P2

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

GnomAD3 exomes AF: 0.235 AC: 58989 AN: 250740 Hom.: 8470 AF XY: 0.228 AC XY: 30952 AN XY: 135468

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 SAS exome AF: 0.0964

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

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0717

Gnomad4 SAS exome AF: 0.0978

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.264

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

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.302

Alfa AF: 0.274 Hom.: 15765

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
MetaRNN	Benign	0.00017	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P
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

Splicing

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

Publications

LitVar

Other links and lift over

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