chr9-127397515-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014580.5(SLC2A8):​c.196G>A​(p.Asp66Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000047 in 1,277,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000047 (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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20979309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A8	NM_014580.5	c.196G>A	p.Asp66Asn	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>A	p.Asp66Asn	missense_variant	Exon 2 of 10	1	NM_014580.5	ENSP00000362469.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000305 AC: 1 AN: 32800 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 19688

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000795

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000470 AC: 6 AN: 1277490 Hom.: 0 Cov.: 32 AF XY: 0.00000319 AC XY: 2 AN XY: 627464

Gnomad4 AFR exome AF: 0.00

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: 0.00000387

Gnomad4 OTH exome AF: 0.0000378

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.14	T;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.58	N;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.21	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.0040	B;.;B
Vest4		0.10
MutPred		0.48		Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP		0.77
MPC		0.19
ClinPred		0.12	T
GERP RS		4.5
Varity_R		0.090
gMVP		0.31

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: rs561202364; hg19: chr9-130159794;