8-109466593-C-T

Position:

• chr8-109466593-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000378402.10(PKHD1L1):​c.8429C>T​(p.Thr2810Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PKHD1L1 ENST00000378402.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2693013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1L1	NM_177531.6	c.8429C>T	p.Thr2810Ile	missense_variant	50/78	ENST00000378402.10	NP_803875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1L1	ENST00000378402.10	c.8429C>T	p.Thr2810Ile	missense_variant	50/78	1	NM_177531.6	ENSP00000367655	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.95	L
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.27
Sift	Benign	0.22	T
Sift4G	Uncertain	0.038	D
Polyphen		0.15	B
Vest4		0.50
MutPred		0.44		Gain of sheet (P = 0.0221);
MVP		0.18
MPC		0.033
ClinPred		0.44	T
GERP RS		6.1
Varity_R		0.11
gMVP		0.46

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

Other links and lift over

dbSNP: rs73313124; hg19: chr8-110478822;