17-7283558-C-G

Variant names:

• chr17-7283558-C-G
• rs8192703
• NM_001042.3:c.236C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001042.3(SLC2A4):​c.236C>G​(p.Thr79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,614,106 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0044 (18 hom.)
• Consequence: SLC2A4 NM_001042.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56
• Publications: 11 publications found

Genes affected

SLC2A4 (HGNC:11009): (solute carrier family 2 member 4) This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]

ENSG00000263342 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007543564).
• BP6: Variant 17-7283558-C-G is Benign according to our data. Variant chr17-7283558-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2647323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042.3. 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
	SLC2A4	NM_001042.3	MANE Select	c.236C>G	p.Thr79Ser	missense	Exon 3 of 11	NP_001033.1	P14672-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4	ENST00000317370.13	TSL:1 MANE Select	c.236C>G	p.Thr79Ser	missense	Exon 3 of 11	ENSP00000320935.8	P14672-1
	SLC2A4	ENST00000572485.5	TSL:1	n.236C>G		non_coding_transcript_exon	Exon 3 of 11	ENSP00000461086.1	P14672-2
	SLC2A4	ENST00000954706.1		c.236C>G	p.Thr79Ser	missense	Exon 3 of 11	ENSP00000624765.1

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 485 AN: 152138 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00350 AC: 881 AN: 251394 AF XY: 0.00354

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00713

Gnomad NFE exome AF: 0.00456

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00436 AC: 6380 AN: 1461850 Hom.: 18 Cov.: 32 AF XY: 0.00437 AC XY: 3179 AN XY: 727222

African (AFR) AF: 0.000777 AC: 26 AN: 33480

American (AMR) AF: 0.00203 AC: 91 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00551 AC: 144 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00150 AC: 129 AN: 86258

European-Finnish (FIN) AF: 0.00706 AC: 377 AN: 53388

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00480 AC: 5333 AN: 1112000

Other (OTH) AF: 0.00452 AC: 273 AN: 60396

GnomAD4 genome AF: 0.00319 AC: 485 AN: 152256 Hom.: 3 Cov.: 31 AF XY: 0.00314 AC XY: 234 AN XY: 74428

African (AFR) AF: 0.000890 AC: 37 AN: 41556

American (AMR) AF: 0.00209 AC: 32 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4818

European-Finnish (FIN) AF: 0.00622 AC: 66 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00450 AC: 306 AN: 68010

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00399 Hom.: 1

Bravo AF: 0.00303

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00453 AC: 39

ExAC AF: 0.00318 AC: 386

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00522

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.65
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-0.82	T
PhyloP100		1.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.10
Sift	Benign	0.64	T
Sift4G	Benign	0.67	T
Polyphen		0.0090	B
Vest4		0.14
MutPred		0.41		Gain of disorder (P = 0.0679)
MVP		0.64
MPC		0.23
ClinPred		0.0035	T
GERP RS		4.2
Varity_R		0.16
gMVP		0.26
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8192703; hg19: chr17-7186877;