chr1-9004794-C-A

Variant names:

• chr1-9004794-C-A
• rs1640628849
• NM_207420.3:c.1278G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_207420.3(SLC2A7):​c.1278G>T​(p.Trp426Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A7 NM_207420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

Genes affected

SLC2A7 (HGNC:13445): (solute carrier family 2 member 7) SLC2A7 belongs to a family of transporters that catalyze the uptake of sugars through facilitated diffusion (Li et al., 2004). This family of transporters shows conservation of 12 transmembrane helices as well as functionally significant amino acid residues (Joost and Thorens, 2001 [PubMed 11780753]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A7	NM_207420.3	c.1278G>T	p.Trp426Cys	missense_variant	Exon 11 of 12	ENST00000400906.2	NP_997303.2
SLC2A7	XM_011540824.3	c.1278G>T	p.Trp426Cys	missense_variant	Exon 11 of 12		XP_011539126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A7	ENST00000400906.2	c.1278G>T	p.Trp426Cys	missense_variant	Exon 11 of 12	1	NM_207420.3	ENSP00000383698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1278G>T (p.W426C) alteration is located in exon 11 (coding exon 11) of the SLC2A7 gene. This alteration results from a G to T substitution at nucleotide position 1278, causing the tryptophan (W) at amino acid position 426 to be replaced by a cysteine (C). 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		7.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-12	D
REVEL	Pathogenic	0.88
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.88		Loss of MoRF binding (P = 0.3474);
MVP		0.64
MPC		0.58
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.85
gMVP		0.92
Mutation Taster		=66/34	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

Publications

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Other links and lift over

dbSNP: rs1640628849; hg19: chr1-9064853;