4-9996816-C-T

Variant names:

• chr4-9996816-C-T
• rs10939650
• NM_020041.3:c.375G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020041.3(SLC2A9):​c.375G>A​(p.Thr125Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,613,598 control chromosomes in the GnomAD database, including 435,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38699 hom., cov: 33)
  • Exomes 𝑓: 0.73 (397299 hom.)
• Consequence: SLC2A9 NM_020041.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.76
• Publications: 42 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 4-9996816-C-T is Benign according to our data. Variant chr4-9996816-C-T is described in ClinVar as Benign. ClinVar VariationId is 350237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020041.3. 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
	SLC2A9	NM_020041.3	MANE Select	c.375G>A	p.Thr125Thr	synonymous	Exon 3 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.288G>A	p.Thr96Thr	synonymous	Exon 4 of 13	NP_001001290.1	Q9NRM0-2
	SLC2A9-AS1	NR_183861.1		n.308-2277C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.375G>A	p.Thr125Thr	synonymous	Exon 3 of 12	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.288G>A	p.Thr96Thr	synonymous	Exon 4 of 13	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.409G>A		non_coding_transcript_exon	Exon 4 of 12

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108052 AN: 152006 Hom.: 38682 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.715

GnomAD2 exomes AF: 0.701 AC: 176022 AN: 251266 AF XY: 0.701

Gnomad AFR exome AF: 0.681

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.507

Gnomad FIN exome AF: 0.735

Gnomad NFE exome AF: 0.753

Gnomad OTH exome AF: 0.711

GnomAD4 exome AF: 0.735 AC: 1074182 AN: 1461474 Hom.: 397299 Cov.: 64 AF XY: 0.733 AC XY: 532679 AN XY: 727048

African (AFR) AF: 0.683 AC: 22860 AN: 33472

American (AMR) AF: 0.662 AC: 29616 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 17449 AN: 26122

East Asian (EAS) AF: 0.501 AC: 19876 AN: 39676

South Asian (SAS) AF: 0.654 AC: 56392 AN: 86244

European-Finnish (FIN) AF: 0.740 AC: 39488 AN: 53396

Middle Eastern (MID) AF: 0.634 AC: 3653 AN: 5764

European-Non Finnish (NFE) AF: 0.757 AC: 841654 AN: 1111714

Other (OTH) AF: 0.715 AC: 43194 AN: 60378

GnomAD4 genome AF: 0.711 AC: 108110 AN: 152124 Hom.: 38699 Cov.: 33 AF XY: 0.706 AC XY: 52463 AN XY: 74352

African (AFR) AF: 0.687 AC: 28491 AN: 41470

American (AMR) AF: 0.657 AC: 10056 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2279 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2611 AN: 5162

South Asian (SAS) AF: 0.640 AC: 3088 AN: 4822

European-Finnish (FIN) AF: 0.735 AC: 7775 AN: 10580

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51384 AN: 68006

Other (OTH) AF: 0.713 AC: 1507 AN: 2114

Alfa AF: 0.733 Hom.: 77802

Bravo AF: 0.705

Asia WGS AF: 0.614 AC: 2137 AN: 3478

EpiCase AF: 0.748

EpiControl AF: 0.739

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hypouricemia, renal, 2 (3)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.3
DANN	Benign	0.79
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs10939650; hg19: chr4-9998440; COSMIC: COSV53318403;