Genetic Variant ENST00000607283.5:n.322-6895G>C (chr3-53099265-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000607283.5(ENSG00000272305):n.71+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

ENSG00000272305
ENST00000607283.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.527

Publications

0 publications found

Variant links:

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)

RFT1 links:

ENSG00000272305 (HGNC:):

ENSG00000272305 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFT1	NM_052859.4 link	c.1208+116A>C		intron_variant	Intron 11 of 12	ENST00000296292.8	NP_443091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFT1	ENST00000296292.8 link	c.1208+116A>C		intron_variant	Intron 11 of 12	1	NM_052859.4	ENSP00000296292.3
ENSG00000272305	ENST00000607283.5 link	n.71+116A>C		intron_variant	Intron 1 of 4	5		ENSP00000475819.1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

588

AN:

152200

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00486

AC XY:

1702

AN XY:

350298

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

17826

American (AMR)

AF:

0.00133

AC:

AN:

36968

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

20212

East Asian (EAS)

AF:

0.00

AC:

AN:

33364

South Asian (SAS)

AF:

0.00256

AC:

169

AN:

65948

European-Finnish (FIN)

AF:

0.00186

AC:

AN:

45698

Middle Eastern (MID)

AF:

0.00239

AC:

AN:

4184

European-Non Finnish (NFE)

AF:

0.00686

AC:

2722

AN:

396512

Other (OTH)

AF:

0.00424

AC:

141

AN:

33292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

171

343

514

686

857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00387

AC:

589

AN:

152318

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41576

American (AMR)

AF:

0.00137

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00311

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00688

AC:

468

AN:

68020

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000905

Hom.:

Bravo

AF:

0.00367

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

(source)

DANN

Benign

0.71

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over