Variant chr3-53088953-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052859.4(RFT1):c.*2950C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,840 control chromosomes in the GnomAD database, including 19,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19673 hom., cov: 31)

Exomes 𝑓: 0.45 ( 6 hom. )

Consequence

RFT1
NM_052859.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.171

Variant links:

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]

RFT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-53088953-G-A is Benign according to our data. Variant chr3-53088953-G-A is described in ClinVar as [Benign]. Clinvar id is 346141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFT1	NM_052859.4 linkuse as main transcript	c.*2950C>T		3_prime_UTR_variant	13/13	ENST00000296292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFT1	ENST00000296292.8 linkuse as main transcript	c.*2950C>T		3_prime_UTR_variant	13/13	1	NM_052859.4	P1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73515

AN:

151684

Hom.:

19667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.521

GnomAD4 exome

AF:

0.450

AC:

AN:

Hom.:

Cov.:

AF XY:

0.458

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.536

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.485

AC:

73548

AN:

151800

Hom.:

19673

Cov.:

AF XY:

0.488

AC XY:

36185

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.727

Gnomad4 SAS

AF:

0.493

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.520

Alfa

AF:

0.529

Hom.:

2811

Bravo

AF:

0.480

Asia WGS

AF:

0.606

AC:

2107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

1.3

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over