17-7283254-C-G

Variant names:

• chr17-7283254-C-G
• NM_001042.3:c.43C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042.3(SLC2A4):​c.43C>G​(p.Pro15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A4 NM_001042.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064980865).

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.43C>G	p.Pro15Ala	missense	Exon 2 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.43C>G	p.Pro15Ala	missense	Exon 2 of 11	ENSP00000320935.8	P14672-1
	SLC2A4	ENST00000572485.5	TSL:1	n.43C>G		non_coding_transcript_exon	Exon 2 of 11	ENSP00000461086.1	P14672-2
	SLC2A4	ENST00000954706.1		c.43C>G	p.Pro15Ala	missense	Exon 2 of 11	ENSP00000624765.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Uncertain	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.94	T
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.065
Sift	Benign	0.047	D
Sift4G	Benign	0.94	T
Polyphen		0.0020	B
Vest4		0.29
MutPred		0.14		Loss of glycosylation at P15 (P = 0.0207)
MVP		0.60
MPC		0.24
ClinPred		0.075	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.057
gMVP		0.54

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

hg19: chr17-7186573;