9-127402608-C-T

Variant names:

• chr9-127402608-C-T
• rs62637572
• NM_014580.5:c.578C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014580.5(SLC2A8):​c.578C>T​(p.Ser193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,595,962 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (19 hom.)
• Consequence: SLC2A8 NM_014580.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004396856).
• BP6: Variant 9-127402608-C-T is Benign according to our data. Variant chr9-127402608-C-T is described in ClinVar as Benign. ClinVar VariationId is 2659501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.578C>T	p.Ser193Phe	missense	Exon 5 of 10	NP_055395.2
	SLC2A8	NM_001271711.2		c.578C>T	p.Ser193Phe	missense	Exon 5 of 9	NP_001258640.1	Q5VVV9
	SLC2A8	NM_001271712.2		c.89C>T	p.Ser30Phe	missense	Exon 3 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.578C>T	p.Ser193Phe	missense	Exon 5 of 10	ENSP00000362469.3	Q9NY64
	SLC2A8	ENST00000373360.7	TSL:1	c.578C>T	p.Ser193Phe	missense	Exon 5 of 9	ENSP00000362458.3	Q5VVV9
	SLC2A8	ENST00000954537.1		c.578C>T	p.Ser193Phe	missense	Exon 5 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152240 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00186 AC: 413 AN: 222046 AF XY: 0.00177

Gnomad AFR exome AF: 0.0000728

Gnomad AMR exome AF: 0.000250

Gnomad ASJ exome AF: 0.0353

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000523

Gnomad OTH exome AF: 0.00219

GnomAD4 exome AF: 0.000980 AC: 1415 AN: 1443604 Hom.: 19 Cov.: 34 AF XY: 0.00103 AC XY: 738 AN XY: 716896

African (AFR) AF: 0.000241 AC: 8 AN: 33238

American (AMR) AF: 0.000210 AC: 9 AN: 42818

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 928 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.000275 AC: 23 AN: 83520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48932

Middle Eastern (MID) AF: 0.00554 AC: 25 AN: 4516

European-Non Finnish (NFE) AF: 0.000254 AC: 281 AN: 1106056

Other (OTH) AF: 0.00236 AC: 141 AN: 59660

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152358 Hom.: 4 Cov.: 33 AF XY: 0.000966 AC XY: 72 AN XY: 74506

African (AFR) AF: 0.0000481 AC: 2 AN: 41592

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00167 Hom.: 8

Bravo AF: 0.000994

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00127 AC: 153

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.27	N
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.18
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.77
MPC		0.21
ClinPred		0.013	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.048
gMVP		0.57
Mutation Taster		=94/6	polymorphism

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: rs62637572; hg19: chr9-130164887; COSMIC: COSV107477606;