9-133473468-G-T

Position:

• chr9-133473468-G-T

Variant summary

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

The NM_017585.4(SLC2A6):​c.1169C>A​(p.Pro390His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A6 NM_017585.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

Genes affected

SLC2A6 (HGNC:11011): (solute carrier family 2 member 6) Hexose transport into mammalian cells is catalyzed by a family of membrane proteins, including SLC2A6, that contain 12 transmembrane domains and a number of critical conserved residues.[supplied by OMIM, Jul 2002]

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/exons	MANE	UniProt
SLC2A6	NM_017585.4	c.1169C>A	p.Pro390His	missense_variant	8/10	ENST00000371899.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A6	ENST00000371899.9	c.1169C>A	p.Pro390His	missense_variant	8/10	1	NM_017585.4	P1
SLC2A6	ENST00000371897.8	c.1037-218C>A		intron_variant		2
SLC2A6	ENST00000485978.1	n.2136C>A		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.1169C>A (p.P390H) alteration is located in exon 8 (coding exon 8) of the SLC2A6 gene. This alteration results from a C to A substitution at nucleotide position 1169, causing the proline (P) at amino acid position 390 to be replaced by a histidine (H). 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	0.11
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.44	N
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.97	D;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.53		Loss of glycosylation at P390 (P = 0.0502);
MVP		0.88
MPC		0.26
ClinPred		0.54	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.43

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: chr9-136338590;