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GeneBe

17-59963150-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016125.4(RNFT1):c.191A>G(p.His64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RNFT1
NM_016125.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07
Variant links:
Genes affected
RNFT1 (HGNC:30206): (ring finger protein, transmembrane 1) Enables ubiquitin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of ERAD pathway and protein autoubiquitination. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.063970804).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNFT1NM_016125.4 linkuse as main transcriptc.191A>G p.His64Arg missense_variant 2/9 ENST00000305783.13
TBC1D3P1-DHX40P1NR_002924.3 linkuse as main transcriptn.1341A>G non_coding_transcript_exon_variant 13/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNFT1ENST00000305783.13 linkuse as main transcriptc.191A>G p.His64Arg missense_variant 2/91 NM_016125.4 P1Q5M7Z0-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152226
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152226
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.0000113
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 05, 2024The c.191A>G (p.H64R) alteration is located in exon 2 (coding exon 2) of the RNFT1 gene. This alteration results from a A to G substitution at nucleotide position 191, causing the histidine (H) at amino acid position 64 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
Cadd
Benign
10
Dann
Benign
0.90
DEOGEN2
Benign
0.026
T;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.064
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.6
N;.
REVEL
Benign
0.037
Sift
Benign
0.93
T;.
Sift4G
Benign
0.33
T;D
Polyphen
0.0
B;.
Vest4
0.22
MutPred
0.22
Gain of solvent accessibility (P = 0.08);Gain of solvent accessibility (P = 0.08);
MVP
0.16
MPC
0.19
ClinPred
0.11
T
GERP RS
4.0
Varity_R
0.089
gMVP
0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1477154765; hg19: chr17-58040511; API