15-35546129-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_080650.4(DPH6):c.13G>C(p.Ala5Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,405,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5S) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 8.0e-7 ( 0 hom. )
Consequence
DPH6
NM_080650.4 missense
NM_080650.4 missense
Scores
10
6
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.84
Publications
0 publications found
Genes affected
DPH6 (HGNC:30543): (diphthamine biosynthesis 6) Enables diphthine-ammonia ligase activity. Predicted to be involved in peptidyl-diphthamide biosynthetic process from peptidyl-histidine. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.924
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_080650.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DPH6 | TSL:1 MANE Select | c.13G>C | p.Ala5Pro | missense | Exon 1 of 9 | ENSP00000256538.4 | Q7L8W6-1 | ||
| DPH6 | TSL:1 | c.13G>C | p.Ala5Pro | missense | Exon 1 of 4 | ENSP00000406976.2 | Q7L8W6-2 | ||
| DPH6 | c.13G>C | p.Ala5Pro | missense | Exon 1 of 9 | ENSP00000566572.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152204
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 7.98e-7 AC: 1AN: 1253542Hom.: 0 Cov.: 30 AF XY: 0.00000163 AC XY: 1AN XY: 613664 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1253542
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
613664
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
26368
American (AMR)
AF:
AC:
1
AN:
24392
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21542
East Asian (EAS)
AF:
AC:
0
AN:
27668
South Asian (SAS)
AF:
AC:
0
AN:
57788
European-Finnish (FIN)
AF:
AC:
0
AN:
42380
Middle Eastern (MID)
AF:
AC:
0
AN:
5130
European-Non Finnish (NFE)
AF:
AC:
0
AN:
997758
Other (OTH)
AF:
AC:
0
AN:
50516
⚠️ 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.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152204
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74358
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41466
American (AMR)
AF:
AC:
1
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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
Genome Het
Variant carriers
0
2
4
6
8
10
<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:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0326)
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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