9-127397248-A-G

Variant names:

• chr9-127397248-A-G
• rs966069923
• NM_014580.5:c.18A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014580.5(SLC2A8):​c.18A>G​(p.Pro6Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000776 in 1,287,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P6P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SLC2A8 NM_014580.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.

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.18A>G	p.Pro6Pro	synonymous	Exon 1 of 10	NP_055395.2
	SLC2A8	NM_001271711.2		c.18A>G	p.Pro6Pro	synonymous	Exon 1 of 9	NP_001258640.1	Q5VVV9
	SLC2A8	NM_001271712.2		c.-102A>G		5_prime_UTR	Exon 1 of 8	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.18A>G	p.Pro6Pro	synonymous	Exon 1 of 10	ENSP00000362469.3	Q9NY64
	SLC2A8	ENST00000373360.7	TSL:1	c.18A>G	p.Pro6Pro	synonymous	Exon 1 of 9	ENSP00000362458.3	Q5VVV9
	SLC2A8	ENST00000954537.1		c.18A>G	p.Pro6Pro	synonymous	Exon 1 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.76e-7 AC: 1 AN: 1287972 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 632820

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25402

American (AMR) AF: 0.00 AC: 0 AN: 18198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20908

East Asian (EAS) AF: 0.00 AC: 0 AN: 28030

South Asian (SAS) AF: 0.00 AC: 0 AN: 67190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4572

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038320

Other (OTH) AF: 0.00 AC: 0 AN: 53296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.46
PhyloP100		-1.0
PromoterAI		-0.019	Neutral

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

dbSNP: rs966069923; hg19: chr9-130159527;