NM_138295.5:c.8096_8105delAAGACTGCCT
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_138295.5(PKD1L1):c.8096_8105delAAGACTGCCT(p.Lys2699ThrfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PKD1L1
NM_138295.5 frameshift
NM_138295.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.448
Publications
0 publications found
Genes affected
PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 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;
PP5
Variant 7-47800736-GAGGCAGTCTT-G is Pathogenic according to our data. Variant chr7-47800736-GAGGCAGTCTT-G is described in ClinVar as Pathogenic. ClinVar VariationId is 3075706.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_138295.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PKD1L1 | MANE Select | c.8096_8105delAAGACTGCCT | p.Lys2699ThrfsTer20 | frameshift | Exon 54 of 57 | NP_612152.1 | Q8TDX9-1 | ||
| PKD1L1-AS1 | n.153+5294_153+5303delAGGCAGTCTT | intron | N/A | ||||||
| PKD1L1-AS1 | n.153+5294_153+5303delAGGCAGTCTT | intron | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PKD1L1 | TSL:1 MANE Select | c.8096_8105delAAGACTGCCT | p.Lys2699ThrfsTer20 | frameshift | Exon 54 of 57 | ENSP00000289672.2 | Q8TDX9-1 | ||
| PKD1L1-AS1 | TSL:1 | n.153+5294_153+5303delAGGCAGTCTT | intron | N/A | |||||
| PKD1L1 | c.8096_8105delAAGACTGCCT | p.Lys2699ThrfsTer20 | frameshift | Exon 54 of 58 | ENSP00000510743.1 | A0A8I5KWV8 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152198
Hom.:
Cov.:
32
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: 6.84e-7 AC: 1AN: 1461892Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727248 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:
1461892
Hom.:
AF XY:
AC XY:
1
AN XY:
727248
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:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60396
⚠️ 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: 0.275
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: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152198
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74352
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41444
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Heterotaxy, visceral, 8, autosomal (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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