17-7285140-C-T

Variant names:

• chr17-7285140-C-T
• rs8192702
• NM_001042.3:c.1073C>T

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.1073C>T​(p.Ala358Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,604,184 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (33 hom.)
• Consequence: SLC2A4 NM_001042.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.01050356).
• BP6: Variant 17-7285140-C-T is Benign according to our data. Variant chr17-7285140-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4	NM_001042.3	MANE Select	c.1073C>T	p.Ala358Val	missense	Exon 9 of 11	NP_001033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4	ENST00000317370.13	TSL:1 MANE Select	c.1073C>T	p.Ala358Val	missense	Exon 9 of 11	ENSP00000320935.8
	SLC2A4	ENST00000572485.5	TSL:1	n.1134C>T		non_coding_transcript_exon	Exon 9 of 11	ENSP00000461086.1
	SLC2A4	ENST00000571308.5	TSL:5	c.1073C>T	p.Ala358Val	missense	Exon 9 of 10	ENSP00000459864.1

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 781 AN: 152214 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000916

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00682

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00597 AC: 1381 AN: 231164 AF XY: 0.00613

Gnomad AFR exome AF: 0.000742

Gnomad AMR exome AF: 0.00306

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0000580

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00736

Gnomad OTH exome AF: 0.00871

GnomAD4 exome AF: 0.00569 AC: 8261 AN: 1451852 Hom.: 33 Cov.: 34 AF XY: 0.00572 AC XY: 4125 AN XY: 721546

African (AFR) AF: 0.000688 AC: 23 AN: 33446

American (AMR) AF: 0.00302 AC: 129 AN: 42668

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 283 AN: 25728

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39406

South Asian (SAS) AF: 0.00286 AC: 242 AN: 84722

European-Finnish (FIN) AF: 0.0127 AC: 650 AN: 51118

Middle Eastern (MID) AF: 0.00783 AC: 45 AN: 5750

European-Non Finnish (NFE) AF: 0.00591 AC: 6553 AN: 1108976

Other (OTH) AF: 0.00558 AC: 335 AN: 60038

GnomAD4 genome AF: 0.00513 AC: 782 AN: 152332 Hom.: 6 Cov.: 32 AF XY: 0.00505 AC XY: 376 AN XY: 74496

African (AFR) AF: 0.000914 AC: 38 AN: 41588

American (AMR) AF: 0.00301 AC: 46 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4830

European-Finnish (FIN) AF: 0.0129 AC: 137 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00682 AC: 464 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00619 Hom.: 10

Bravo AF: 0.00404

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00709 AC: 61

ExAC AF: 0.00574 AC: 696

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.43	T
PhyloP100		0.49
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Benign	0.097	T
Sift4G	Benign	0.54	T
Polyphen		0.17	B
Vest4		0.65
MVP		0.79
MPC		0.28
ClinPred		0.029	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.49
Mutation Taster		=94/6	polymorphism

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: rs8192702; hg19: chr17-7188459; COSMIC: COSV107205602;