rs202169457

Variant summary

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

The NM_177531.6(PKHD1L1):​c.628G>A​(p.Gly210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,590 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. G210R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PKHD1L1
NM_177531.6 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.78
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.628G>A p.Gly210Ser missense_variant Exon 8 of 78 ENST00000378402.10 NP_803875.2 Q86WI1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKHD1L1ENST00000378402.10 linkc.628G>A p.Gly210Ser missense_variant Exon 8 of 78 1 NM_177531.6 ENSP00000367655.5 Q86WI1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1445590
Hom.:
0
Cov.:
28
AF XY:
0.00000139
AC XY:
1
AN XY:
719738
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.08e-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
0.10
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.44
T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.15
Sift
Benign
0.15
T
Sift4G
Benign
0.062
T
Polyphen
0.84
P
Vest4
0.52
MutPred
0.42
Gain of disorder (P = 0.0715);
MVP
0.30
MPC
0.075
ClinPred
0.92
D
GERP RS
5.4
Varity_R
0.16
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-110401312; API