rs2564921

chr3-53091569-T-Cchr3-53091569-T-G

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.*334A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 315,340 control chromosomes in the GnomAD database, including 44,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19831 hom., cov: 32)
  • Exomes 𝑓: 0.54 (24422 hom.)
• Consequence: RFT1 NM_052859.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.53

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 3-53091569-T-C is Benign according to our data. Variant chr3-53091569-T-C is described in ClinVar as [Benign]. Clinvar id is 346177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFT1	NM_052859.4	c.*334A>G		3_prime_UTR_variant	13/13	ENST00000296292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFT1	ENST00000296292.8	c.*334A>G		3_prime_UTR_variant	13/13	1	NM_052859.4	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73839 AN: 151914 Hom.: 19825 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.537 AC: 87632 AN: 163308 Hom.: 24422 Cov.: 0 AF XY: 0.532 AC XY: 46260 AN XY: 87008

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.633

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.486 AC: 73872 AN: 152032 Hom.: 19831 Cov.: 32 AF XY: 0.490 AC XY: 36387 AN XY: 74326

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.520

Alfa AF: 0.545 Hom.: 10245

Bravo AF: 0.481

Asia WGS AF: 0.605 AC: 2104 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	0.056
Dann	Benign	0.37

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: rs2564921; hg19: chr3-53125585;