8-109382539-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5
The NM_177531.6(PKHD1L1):c.385G>A(p.Gly129Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
PKHD1L1
NM_177531.6 missense
NM_177531.6 missense
Scores
1
11
6
Clinical Significance
Conservation
PhyloP100: 4.50
Publications
3 publications found
Genes affected
PKHD1L1 (HGNC:20313): (PKHD1 like 1) Predicted to act upstream of or within sensory perception of sound. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
PKHD1L1 Gene-Disease associations (from GenCC):
- autosomal recessive nonsyndromic hearing loss 124Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
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 8-109382539-G-A is Pathogenic according to our data. Variant chr8-109382539-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 3220942.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_177531.6. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152068
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 Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74296 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152068
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74296
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67998
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
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Autosomal recessive nonsyndromic hearing loss 124 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0961)
MVP
MPC
ClinPred
D
GERP RS
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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