rs796053522

Variant names:

• chr3-53092605-T-A
• NM_052859.4:c.1222A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-53092605-T-A
• chr3-53092605-T-C

Variant summary

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

The NM_052859.4(RFT1):​c.1222A>T​(p.Met408Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,392 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RFT1 NM_052859.4 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000272305 (HGNC:):

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 rank	MANE	Protein	UniProt
RFT1	NM_052859.4	c.1222A>T	p.Met408Leu	missense_variant	Exon 12 of 13	ENST00000296292.8	NP_443091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFT1	ENST00000296292.8	c.1222A>T	p.Met408Leu	missense_variant	Exon 12 of 13	1	NM_052859.4	ENSP00000296292.3
ENSG00000272305	ENST00000607283.5	n.85A>T		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000475819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459392 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 725640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.072
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.41
Sift	Benign	0.18	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.26	B;B
Vest4		0.49
MutPred		0.68		Gain of catalytic residue at M408 (P = 0.2661);.;
MVP		0.88
MPC		0.30
ClinPred		0.89	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr3-53126621;