3-53084723-C-T

Variant names:

• chr3-53084723-C-T
• rs2336725
• ENST00000607283.5:n.322-6895G>A

Variant summary

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

The ENST00000607283.5(ENSG00000272305):​n.322-6895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,082 control chromosomes in the GnomAD database, including 19,777 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 0.49 (19777 hom., cov: 33)
• Consequence: ENSG00000272305 ENST00000607283.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 69 publications found

Genes affected

ENSG00000272305 (HGNC:):

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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607283.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272305	ENST00000607283.5	TSL:5	n.322-6895G>A		intron	N/A	ENSP00000475819.1	U3KQE9
	RFT1	ENST00000850556.1		c.1209-6895G>A		intron	N/A	ENSP00000520849.1	A0ABB0MVK0
	ENSG00000272305	ENST00000607203.1	TSL:5	n.*99+1027G>A		intron	N/A	ENSP00000475866.1	U3KQG8

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73733 AN: 151962 Hom.: 19771 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.485 AC: 73766 AN: 152082 Hom.: 19777 Cov.: 33 AF XY: 0.489 AC XY: 36336 AN XY: 74336

African (AFR) AF: 0.244 AC: 10134 AN: 41478

American (AMR) AF: 0.577 AC: 8815 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2239 AN: 3466

East Asian (EAS) AF: 0.728 AC: 3763 AN: 5172

South Asian (SAS) AF: 0.495 AC: 2384 AN: 4820

European-Finnish (FIN) AF: 0.585 AC: 6192 AN: 10576

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38331 AN: 67968

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.543 Hom.: 79084

Bravo AF: 0.480

Asia WGS AF: 0.607 AC: 2108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.2
DANN	Benign	0.69
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2336725; hg19: chr3-53118739;