8-109384122-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177531.6(PKHD1L1):​c.470C>T​(p.Thr157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. T157N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PKHD1L1
NM_177531.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.425
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12004009).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKHD1L1NM_177531.6 linkc.470C>T p.Thr157Ile missense_variant Exon 5 of 78 ENST00000378402.10 NP_803875.2 Q86WI1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKHD1L1ENST00000378402.10 linkc.470C>T p.Thr157Ile missense_variant Exon 5 of 78 1 NM_177531.6 ENSP00000367655.5 Q86WI1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.040
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.054
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.17
Sift
Benign
0.44
T
Sift4G
Benign
0.30
T
Polyphen
0.15
B
Vest4
0.36
MutPred
0.48
Loss of sheet (P = 0.0043);
MVP
0.23
MPC
0.056
ClinPred
0.83
D
GERP RS
3.9
Varity_R
0.052
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373444015; hg19: chr8-110396351; API