rs2564921

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-53091569-T-A
• chr3-53091569-T-C
• chr3-53091569-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052859.4(RFT1):​c.*334A>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 0.0000061 in 164,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: RFT1 NM_052859.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.*334A>T		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>T		3_prime_UTR	Exon 13 of 13	ENSP00000296292.3
	ENSG00000272305	ENST00000607283.5	TSL:5	n.321+800A>T		intron	N/A	ENSP00000475819.1
	RFT1	ENST00000850556.1		c.1208+7812A>T		intron	N/A	ENSP00000520849.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000610 AC: 1 AN: 164036 Hom.: 0 Cov.: 0 AF XY: 0.0000114 AC XY: 1 AN XY: 87438

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5714

American (AMR) AF: 0.00 AC: 0 AN: 8498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4262

East Asian (EAS) AF: 0.00 AC: 0 AN: 8422

South Asian (SAS) AF: 0.0000373 AC: 1 AN: 26774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 94196

Other (OTH) AF: 0.00 AC: 0 AN: 8588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.042
DANN	Benign	0.44
PhyloP100		-2.5

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;