rs1135402756
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PVS1PM2PP3_ModeratePP5
The NM_173543.3(DZIP1L):c.1061_1062delAG(p.Glu354fs) variant causes a frameshift, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DZIP1L
NM_173543.3 frameshift, splice_region
NM_173543.3 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.09
Publications
2 publications found
Genes affected
DZIP1L (HGNC:26551): (DAZ interacting zinc finger protein 1 like) Predicted to enable metal ion binding activity. Involved in cilium assembly and regulation of protein localization. Located in ciliary basal body. Colocalizes with centriole. Implicated in polycystic kidney disease 5. [provided by Alliance of Genome Resources, Apr 2022]
DZIP1L Gene-Disease associations (from GenCC):
- autosomal recessive polycystic kidney diseaseInheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- polycystic kidney disease 5Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 13 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 3-138086960-CCT-C is Pathogenic according to our data. Variant chr3-138086960-CCT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 431434.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_173543.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DZIP1L | NM_173543.3 | MANE Select | c.1061_1062delAG | p.Glu354fs | frameshift splice_region | Exon 7 of 16 | NP_775814.2 | ||
| DZIP1L | NM_001170538.1 | c.1061_1062delAG | p.Glu354fs | frameshift splice_region | Exon 8 of 14 | NP_001164009.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DZIP1L | ENST00000327532.7 | TSL:1 MANE Select | c.1061_1062delAG | p.Glu354fs | frameshift splice_region | Exon 7 of 16 | ENSP00000332148.2 | ||
| DZIP1L | ENST00000851674.1 | c.1061_1062delAG | p.Glu354fs | frameshift splice_region | Exon 7 of 16 | ENSP00000521733.1 | |||
| DZIP1L | ENST00000912002.1 | c.1061_1062delAG | p.Glu354fs | frameshift splice_region | Exon 7 of 16 | ENSP00000582061.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2AN: 1461454Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727042 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1461454
Hom.:
AF XY:
AC XY:
1
AN XY:
727042
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33432
American (AMR)
AF:
AC:
2
AN:
44624
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26122
East Asian (EAS)
AF:
AC:
0
AN:
39662
South Asian (SAS)
AF:
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111880
Other (OTH)
AF:
AC:
0
AN:
60366
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
Exome 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
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Polycystic kidney disease 5 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 3
DS_DL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.