8-109388516-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_177531.6(PKHD1L1):​c.589C>T​(p.Pro197Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,365,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P197T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

PKHD1L1
NM_177531.6 missense

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKHD1L1NM_177531.6 linkc.589C>T p.Pro197Ser missense_variant Exon 7 of 78 ENST00000378402.10 NP_803875.2 Q86WI1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKHD1L1ENST00000378402.10 linkc.589C>T p.Pro197Ser missense_variant Exon 7 of 78 1 NM_177531.6 ENSP00000367655.5 Q86WI1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000645
AC:
1
AN:
155040
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81956
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000450
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000220
AC:
3
AN:
1365994
Hom.:
0
Cov.:
28
AF XY:
0.00000296
AC XY:
2
AN XY:
675504
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000256
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.52e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Uncertain
0.025
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Uncertain
0.088
D
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.51
Sift
Benign
0.22
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.43
MutPred
0.62
Gain of relative solvent accessibility (P = 0.1066);
MVP
0.31
MPC
0.086
ClinPred
0.93
D
GERP RS
4.5
Varity_R
0.26
gMVP
0.51

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: rs1305424419; hg19: chr8-110400745; COSMIC: COSV65741012; API