chr3-53089016-C-T

Position:

• chr3-53089016-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_052859.4(RFT1):​c.*2887G>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 0.662 in 151,418 control chromosomes in the GnomAD database, including 33,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33513 hom., cov: 29)
  • Exomes 𝑓: 0.63 (28 hom.)
• Consequence: RFT1 NM_052859.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 3-53089016-C-T is Benign according to our data. Variant chr3-53089016-C-T is described in ClinVar as [Benign]. Clinvar id is 346142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFT1	NM_052859.4	c.*2887G>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.*2887G>A		3_prime_UTR_variant	13/13	1	NM_052859.4	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100030 AN: 151154 Hom.: 33469 Cov.: 29

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.634 AC: 90 AN: 142 Hom.: 28 Cov.: 0 AF XY: 0.655 AC XY: 72 AN XY: 110

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.662 AC: 100132 AN: 151276 Hom.: 33513 Cov.: 29 AF XY: 0.665 AC XY: 49128 AN XY: 73870

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.685

Alfa AF: 0.663 Hom.: 4169

Bravo AF: 0.667

Asia WGS AF: 0.814 AC: 2828 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	-1.0
CADD	Benign	1.7
DANN	Benign	0.42

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: rs2099162; hg19: chr3-53123032;