NM_014580.5:c.196G>C

Variant names:

• chr9-127397515-G-C
• rs561202364
• NM_014580.5:c.196G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014580.5(SLC2A8):​c.196G>C​(p.Asp66His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,774 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D66Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SLC2A8 NM_014580.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 0 publications found

Genes affected

SLC2A8 (HGNC:13812): (solute carrier family 2 member 8) This gene belongs to the solute carrier 2A family, which includes intracellular glucose transporters. Based on sequence comparison, the glucose transporters are grouped into three classes and this gene is a member of class II. The encoded protein, like other members of the family, contains several conserved residues and motifs and 12 transmembrane domains with both amino and carboxyl ends being on the cytosolic side of the membrane. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014580.5. 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
	SLC2A8	NM_014580.5	MANE Select	c.196G>C	p.Asp66His	missense	Exon 2 of 10	NP_055395.2
	SLC2A8	NM_001271711.2		c.196G>C	p.Asp66His	missense	Exon 2 of 9	NP_001258640.1	Q5VVV9
	SLC2A8	NM_001271712.2		c.-64+229G>C		intron	N/A	NP_001258641.1	A0A087WT42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A8	ENST00000373371.8	TSL:1 MANE Select	c.196G>C	p.Asp66His	missense	Exon 2 of 10	ENSP00000362469.3	Q9NY64
	SLC2A8	ENST00000373360.7	TSL:1	c.196G>C	p.Asp66His	missense	Exon 2 of 9	ENSP00000362458.3	Q5VVV9
	SLC2A8	ENST00000954537.1		c.196G>C	p.Asp66His	missense	Exon 2 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.83e-7 AC: 1 AN: 1277490 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 627464

African (AFR) AF: 0.0000402 AC: 1 AN: 24904

American (AMR) AF: 0.00 AC: 0 AN: 16580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20048

East Asian (EAS) AF: 0.00 AC: 0 AN: 28434

South Asian (SAS) AF: 0.00 AC: 0 AN: 64450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3938

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1034718

Other (OTH) AF: 0.00 AC: 0 AN: 52976

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152284 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74468

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.75
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.094
Eigen_PC	Benign	0.0051
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.56
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.30
Sift	Benign	0.096	T
Sift4G	Benign	0.12	T
Polyphen		0.66	P
Vest4		0.21
MutPred		0.52		Gain of helix (P = 0.0143)
MVP		0.81
MPC		0.63
ClinPred		0.75	D
GERP RS		4.5
PromoterAI		-0.11	Neutral
Varity_R		0.12
gMVP		0.48
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs561202364; hg19: chr9-130159794;