3-53091569-T-C

Variant names:

• chr3-53091569-T-C
• rs2564921
• NM_052859.4:c.*334A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000296292.8(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 ENST00000296292.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.53
• Publications: 37 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 -20 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 VariationId is 346177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296292.8. 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.*334A>G		3_prime_UTR	Exon 13 of 13	NP_443091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFT1	ENST00000296292.8	TSL:1 MANE Select	c.*334A>G		3_prime_UTR	Exon 13 of 13	ENSP00000296292.3
	ENSG00000272305	ENST00000607283.5	TSL:5	n.321+800A>G		intron	N/A	ENSP00000475819.1
	RFT1	ENST00000850556.1		c.1208+7812A>G		intron	N/A	ENSP00000520849.1

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

African (AFR) AF: 0.238 AC: 1358 AN: 5696

American (AMR) AF: 0.605 AC: 5122 AN: 8470

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2679 AN: 4230

East Asian (EAS) AF: 0.735 AC: 6174 AN: 8396

South Asian (SAS) AF: 0.468 AC: 12465 AN: 26622

European-Finnish (FIN) AF: 0.569 AC: 3933 AN: 6910

Middle Eastern (MID) AF: 0.490 AC: 308 AN: 628

European-Non Finnish (NFE) AF: 0.544 AC: 50988 AN: 93802

Other (OTH) AF: 0.538 AC: 4605 AN: 8554

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

African (AFR) AF: 0.245 AC: 10164 AN: 41496

American (AMR) AF: 0.577 AC: 8810 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3766 AN: 5180

South Asian (SAS) AF: 0.494 AC: 2377 AN: 4816

European-Finnish (FIN) AF: 0.586 AC: 6175 AN: 10540

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38436 AN: 67948

Other (OTH) AF: 0.520 AC: 1098 AN: 2112

Alfa AF: 0.534 Hom.: 41944

Bravo AF: 0.481

Asia WGS AF: 0.605 AC: 2104 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	RFT1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.056
DANN	Benign	0.37
PhyloP100		-2.5
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: rs2564921; hg19: chr3-53125585;