17-7285140-C-T

Variant summary

Our verdict is Benign. Variant got -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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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 id is 2647324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A4	NM_001042.3	c.1073C>T	p.Ala358Val	missense_variant	9/11	ENST00000317370.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A4	ENST00000317370.13	c.1073C>T	p.Ala358Val	missense_variant	9/11	1	NM_001042.3	P1

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

GnomAD3 exomes AF: 0.00597 AC: 1381 AN: 231164 Hom.: 8 AF XY: 0.00613 AC XY: 765 AN XY: 124834

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 SAS exome AF: 0.00292

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

Gnomad4 AFR exome AF: 0.000688

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00286

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.00591

Gnomad4 OTH exome AF: 0.00558

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

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00651 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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

SLC2A4: BS2 -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.89	D;D;D
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-0.43	T
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N;.;N
REVEL	Benign	0.16
Sift	Benign	0.097	T;.;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.17	B;.;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

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: rs8192702; hg19: chr17-7188459;