rs121434581

Variant names:

• chr17-7285729-G-A
• rs121434581
• NM_001042.3:c.1147G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7285729-G-A
• chr17-7285729-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001042.3(SLC2A4):​c.1147G>A​(p.Val383Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,614,176 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (30 hom.)
• Consequence: SLC2A4 NM_001042.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.253

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009615719).
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A4	NM_001042.3	c.1147G>A	p.Val383Ile	missense_variant	Exon 10 of 11	ENST00000317370.13	NP_001033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A4	ENST00000317370.13	c.1147G>A	p.Val383Ile	missense_variant	Exon 10 of 11	1	NM_001042.3	ENSP00000320935.8

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 615 AN: 152182 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00610

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00417 AC: 1049 AN: 251460 AF XY: 0.00432

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00405

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00577 AC: 8430 AN: 1461876 Hom.: 30 Cov.: 32 AF XY: 0.00565 AC XY: 4107 AN XY: 727244

Gnomad4 AFR exome AF: 0.000627 AC: 21 AN: 33476

Gnomad4 AMR exome AF: 0.00470 AC: 210 AN: 44724

Gnomad4 ASJ exome AF: 0.0131 AC: 342 AN: 26136

Gnomad4 EAS exome AF: 0.0000504 AC: 2 AN: 39700

Gnomad4 SAS exome AF: 0.00253 AC: 218 AN: 86258

Gnomad4 FIN exome AF: 0.000487 AC: 26 AN: 53420

Gnomad4 NFE exome AF: 0.00647 AC: 7199 AN: 1112002

Gnomad4 Remaining exome AF: 0.00618 AC: 373 AN: 60392

GnomAD4 genome AF: 0.00404 AC: 615 AN: 152300 Hom.: 3 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74478

Gnomad4 AFR AF: 0.00103 AC: 0.0010349 AN: 0.0010349

Gnomad4 AMR AF: 0.00529 AC: 0.00529273 AN: 0.00529273

Gnomad4 ASJ AF: 0.0153 AC: 0.015265 AN: 0.015265

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00248 AC: 0.00248447 AN: 0.00248447

Gnomad4 FIN AF: 0.0000942 AC: 0.0000942329 AN: 0.0000942329

Gnomad4 NFE AF: 0.00610 AC: 0.00609989 AN: 0.00609989

Gnomad4 OTH AF: 0.00426 AC: 0.00425733 AN: 0.00425733

Alfa AF: 0.00545 Hom.: 7

Bravo AF: 0.00492

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00500 AC: 43

ExAC AF: 0.00419 AC: 509

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00687

EpiControl AF: 0.00682

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC2A4: BP4, BS2 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Type 2 diabetes mellitus Uncertain:1

Jan 01, 1995

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.088	T;T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.0096	T;T;T
MetaSVM	Benign	-0.71	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.13	N;.;N
REVEL	Uncertain	0.39
Sift	Benign	0.38	T;.;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.010	B;.;B
Vest4		0.062
MVP		0.66
MPC		0.21
ClinPred		0.0088	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.079
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs121434581; hg19: chr17-7189048;