NM_052859.4:c.1208+116A>C

Variant names:

• chr3-53099265-T-G
• rs139206390
• NM_052859.4:c.1208+116A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_052859.4(RFT1):​c.1208+116A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 806,322 control chromosomes in the GnomAD database, including 36 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 0.0039 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (32 hom.)
• Consequence: RFT1 NM_052859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 0 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)

ENSG00000272305 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00387 (589/152318) while in subpopulation NFE AF = 0.00688 (468/68020). AF 95% confidence interval is 0.00637. There are 4 homozygotes in GnomAd4. There are 262 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.1208+116A>C		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.1208+116A>C		intron	N/A	ENSP00000296292.3
	ENSG00000272305	ENST00000607283.5	TSL:5	n.71+116A>C		intron	N/A	ENSP00000475819.1
	RFT1	ENST00000394738.7	TSL:5	c.1091+116A>C		intron	N/A	ENSP00000378223.3

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 588 AN: 152200 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00688

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00494 AC: 3230 AN: 654004 Hom.: 32 AF XY: 0.00486 AC XY: 1702 AN XY: 350298

African (AFR) AF: 0.00168 AC: 30 AN: 17826

American (AMR) AF: 0.00133 AC: 49 AN: 36968

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 24 AN: 20212

East Asian (EAS) AF: 0.00 AC: 0 AN: 33364

South Asian (SAS) AF: 0.00256 AC: 169 AN: 65948

European-Finnish (FIN) AF: 0.00186 AC: 85 AN: 45698

Middle Eastern (MID) AF: 0.00239 AC: 10 AN: 4184

European-Non Finnish (NFE) AF: 0.00686 AC: 2722 AN: 396512

Other (OTH) AF: 0.00424 AC: 141 AN: 33292

GnomAD4 genome AF: 0.00387 AC: 589 AN: 152318 Hom.: 4 Cov.: 32 AF XY: 0.00352 AC XY: 262 AN XY: 74486

African (AFR) AF: 0.00125 AC: 52 AN: 41576

American (AMR) AF: 0.00137 AC: 21 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4818

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00688 AC: 468 AN: 68020

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.000905 Hom.: 0

Bravo AF: 0.00367

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

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: rs139206390; hg19: chr3-53133281;