NM_018840.5:c.75G>A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5
The NM_018840.5(RAB5IF):c.75G>A(p.Trp25*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,376,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
RAB5IF
NM_018840.5 stop_gained
NM_018840.5 stop_gained
Scores
5
2
2
Clinical Significance
Conservation
PhyloP100: 7.60
Publications
1 publications found
Genes affected
RAB5IF (HGNC:15870): (RAB5 interacting factor) Involved in mitochondrial respirasome assembly. Located in mitochondrial respirasome. [provided by Alliance of Genome Resources, Apr 2022]
TGIF2-RAB5IF (HGNC:44664): (TGIF2-RAB5IF readthrough) This locus represents naturally occurring read-through transcription between the neighboring TGIF2 (TGFB-induced factor homeobox 2) and C20orf24 (chromosome 20 open reading frame 24) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 20-36606026-G-A is Pathogenic according to our data. Variant chr20-36606026-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 996015.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018840.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RAB5IF | NM_018840.5 | MANE Select | c.75G>A | p.Trp25* | stop_gained | Exon 1 of 4 | NP_061328.1 | Q9BUV8-2 | |
| RAB5IF | NM_199483.3 | c.75G>A | p.Trp25* | stop_gained | Exon 1 of 3 | NP_955777.1 | Q9BUV8-5 | ||
| RAB5IF | NM_001199534.2 | c.75G>A | p.Trp25* | stop_gained | Exon 1 of 4 | NP_001186463.1 | Q9BUV8-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RAB5IF | ENST00000344795.8 | TSL:1 MANE Select | c.75G>A | p.Trp25* | stop_gained | Exon 1 of 4 | ENSP00000340164.3 | Q9BUV8-2 | |
| RAB5IF | ENST00000373852.9 | TSL:1 | c.75G>A | p.Trp25* | stop_gained | Exon 1 of 4 | ENSP00000362958.5 | Q9BUV8-1 | |
| TGIF2-RAB5IF | ENST00000558530.1 | TSL:3 | c.193-1689G>A | intron | N/A | ENSP00000454021.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00 AC: 0AN: 139994 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
139994
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000145 AC: 2AN: 1376112Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1AN XY: 678256 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1376112
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
678256
show subpopulations
African (AFR)
AF:
AC:
0
AN:
29778
American (AMR)
AF:
AC:
0
AN:
34148
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24602
East Asian (EAS)
AF:
AC:
0
AN:
33744
South Asian (SAS)
AF:
AC:
0
AN:
76648
European-Finnish (FIN)
AF:
AC:
0
AN:
48960
Middle Eastern (MID)
AF:
AC:
0
AN:
5072
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1066354
Other (OTH)
AF:
AC:
1
AN:
56806
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.650
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
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65-70
70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 (1)
1
-
-
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2 (1)
1
-
-
Hypertelorism;C0025990:Micrognathia;C0036439:Scoliosis;C0265695:Rib fusion;C1398522:Bilateral cleft lip and palate;C1853241:Flat face;C2243051:Macrocephaly;C3714756:Intellectual disability;C4021789:Abnormality of the vertebral column;C4721788:Bifid ribs (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Pathogenic
D
PhyloP100
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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