3-53089063-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052859.4(RFT1):c.*2840T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,036 control chromosomes in the GnomAD database, including 2,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2842 hom., cov: 31)
  • Exomes 𝑓: 0.092 (1 hom.)
• Consequence: RFT1 NM_052859.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.164

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-53089063-A-T is Benign according to our data. Variant chr3-53089063-A-T is described in ClinVar as [Benign]. Clinvar id is 346143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFT1	NM_052859.4	c.*2840T>A		3_prime_UTR_variant	13/13	ENST00000296292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFT1	ENST00000296292.8	c.*2840T>A		3_prime_UTR_variant	13/13	1	NM_052859.4	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24388 AN: 151820 Hom.: 2820 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0971

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0918 AC: 9 AN: 98 Hom.: 1 Cov.: 0 AF XY: 0.0735 AC XY: 5 AN XY: 68

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0513

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.161 AC: 24459 AN: 151938 Hom.: 2842 Cov.: 31 AF XY: 0.156 AC XY: 11592 AN XY: 74282

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0971

Gnomad4 OTH AF: 0.154

Alfa AF: 0.129 Hom.: 251

Bravo AF: 0.176

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RFT1-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.55

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: rs9875573; hg19: chr3-53123079;