rs73313124

Positions:

• chr8-109466593-C-A
• chr8-109466593-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_177531.6(PKHD1L1):​c.8429C>A​(p.Thr2810Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,596,582 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.0025 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00031 (3 hom.)
• Consequence: PKHD1L1 NM_177531.6 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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008990943).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1L1	NM_177531.6	c.8429C>A	p.Thr2810Asn	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>A	p.Thr2810Asn	missense_variant	50/78	1	NM_177531.6	ENSP00000367655	P1

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152038 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00790

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000643 AC: 149 AN: 231886 Hom.: 0 AF XY: 0.000551 AC XY: 69 AN XY: 125164

Gnomad AFR exome AF: 0.00779

Gnomad AMR exome AF: 0.000872

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000472

Gnomad OTH exome AF: 0.000524

GnomAD4 exome AF: 0.000307 AC: 443 AN: 1444426 Hom.: 3 Cov.: 30 AF XY: 0.000290 AC XY: 208 AN XY: 716532

Gnomad4 AFR exome AF: 0.00869

Gnomad4 AMR exome AF: 0.000969

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000471

Gnomad4 OTH exome AF: 0.000887

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152156 Hom.: 2 Cov.: 31 AF XY: 0.00266 AC XY: 198 AN XY: 74378

Gnomad4 AFR AF: 0.00814

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000431 Hom.: 1

Bravo AF: 0.00307

ESP6500AA AF: 0.00777 AC: 30

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000737 AC: 89

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.059
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Benign	0.092	T
Sift4G	Benign	0.092	T
Polyphen		0.29	B
Vest4		0.46
MVP		0.20
MPC		0.042
ClinPred		0.011	T
GERP RS		6.1
Varity_R		0.10
gMVP		0.49

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;