8-109384122-C-T

Variant names:

• chr8-109384122-C-T
• rs373444015
• NM_177531.6:c.470C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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 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
PKHD1L1	NM_177531.6	c.470C>T	p.Thr157Ile	missense_variant	Exon 5 of 78	ENST00000378402.10	NP_803875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1L1	ENST00000378402.10	c.470C>T	p.Thr157Ile	missense_variant	Exon 5 of 78	1	NM_177531.6	ENSP00000367655.5

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

Other links and lift over

dbSNP: rs373444015; hg19: chr8-110396351;