3-53092605-T-C

Position:

• chr3-53092605-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_052859.4(RFT1):​c.1222A>G​(p.Met408Val) variant causes a missense change. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RFT1 NM_052859.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.76

Genes affected

RFT1 (HGNC:30220): (RFT1 homolog) This gene encodes an enzyme which catalyzes the translocation of the Man(5)GlcNAc (2)-PP-Dol intermediate from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane in the pathway for the N-glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type In.[provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914
• PP5: Variant 3-53092605-T-C is Pathogenic according to our data. Variant chr3-53092605-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 207990.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFT1	NM_052859.4	c.1222A>G	p.Met408Val	missense_variant	12/13	ENST00000296292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFT1	ENST00000296292.8	c.1222A>G	p.Met408Val	missense_variant	12/13	1	NM_052859.4	P1
RFT1	ENST00000394738.7	c.1105A>G	p.Met369Val	missense_variant	11/12	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

RFT1-congenital disorder of glycosylation Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D;D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Pathogenic	3.7	H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.93	P;D
Vest4		0.95
MutPred		0.66		Gain of loop (P = 0.069);.;
MVP		0.93
MPC		0.55
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.50
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs796053522; hg19: chr3-53126621;