20-46726270-G-C

Position:

• chr20-46726270-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030777.4(SLC2A10):​c.1234G>C​(p.Ala412Pro) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A10 NM_030777.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

Genes affected

SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.1234G>C	p.Ala412Pro	missense_variant	2/5	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.1234G>C	p.Ala412Pro	missense_variant	2/5	1	NM_030777.4	ENSP00000352216.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.92	L
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.48
Sift	Benign	0.048	D
Sift4G	Benign	0.089	T
Polyphen		0.98	D
Vest4		0.54
MutPred		0.83		Loss of catalytic residue at A412 (P = 0.1179);
MVP		0.78
MPC		0.42
ClinPred		0.51	D
GERP RS		2.5
Varity_R		0.44
gMVP		0.81

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

LitVar

Other links and lift over

dbSNP: rs746203433; hg19: chr20-45354909;