9-127397249-G-C

Variant names:

• chr9-127397249-G-C
• NM_014580.5:c.19G>C

Variant summary

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

The NM_014580.5(SLC2A8):​c.19G>C​(p.Glu7Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC2A8 NM_014580.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.218

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=0.17967221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A8	NM_014580.5	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 10	ENST00000373371.8	NP_055395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A8	ENST00000373371.8	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 10	1	NM_014580.5	ENSP00000362469.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1286622 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 631998

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>C (p.E7Q) alteration is located in exon 1 (coding exon 1) of the SLC2A8 gene. This alteration results from a G to C substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.097	T;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.19	T;D;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.13
MVP		0.78
MPC		0.19
ClinPred		0.18	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.086
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130159528;