rs13088281

Variant names:

• chr3-53113560-C-A
• rs13088281
• NM_052859.4:c.697-1652G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052859.4(RFT1):​c.697-1652G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,254 control chromosomes in the GnomAD database, including 565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (565 hom., cov: 33)
• Consequence: RFT1 NM_052859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• RFT1-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFT1	NM_052859.4	MANE Select	c.697-1652G>T		intron	N/A	NP_443091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFT1	ENST00000296292.8	TSL:1 MANE Select	c.697-1652G>T		intron	N/A	ENSP00000296292.3
	RFT1	ENST00000394738.7	TSL:5	c.580-1652G>T		intron	N/A	ENSP00000378223.3
	RFT1	ENST00000850556.1		c.697-1652G>T		intron	N/A	ENSP00000520849.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11821 AN: 152136 Hom.: 561 Cov.: 33

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0943

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0777 AC: 11829 AN: 152254 Hom.: 565 Cov.: 33 AF XY: 0.0770 AC XY: 5730 AN XY: 74426

African (AFR) AF: 0.0229 AC: 952 AN: 41560

American (AMR) AF: 0.0952 AC: 1457 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3470

East Asian (EAS) AF: 0.120 AC: 620 AN: 5184

South Asian (SAS) AF: 0.0909 AC: 439 AN: 4828

European-Finnish (FIN) AF: 0.0834 AC: 883 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6904 AN: 68014

Other (OTH) AF: 0.0972 AC: 205 AN: 2110

Alfa AF: 0.0942 Hom.: 1887

Bravo AF: 0.0767

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.4
DANN	Benign	0.76
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13088281; hg19: chr3-53147576;