9-127397515-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A8	NM_014580.5	c.196G>C	p.Asp66His	missense_variant	Exon 2 of 10	ENST00000373371.8	NP_055395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A8	ENST00000373371.8	c.196G>C	p.Asp66His	missense_variant	Exon 2 of 10	1	NM_014580.5	ENSP00000362469.3

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

Gnomad4 AFR exome AF: 0.0000402

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	0.094
Eigen_PC	Benign	0.0051
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D;T;D
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.096	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.66	P;.;P
Vest4		0.21
MutPred		0.52		Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP		0.81
MPC		0.63
ClinPred		0.75	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130159794;