chr6-52066088-T-TA

Position:

• chr6-52066088-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_138694.4(PKHD1):​c.779-12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (35007 hom., cov: 0)
  • Exomes 𝑓: 0.44 (4297 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.169

Genes affected

PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

PKHD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-52066088-T-TA is Benign according to our data. Variant chr6-52066088-T-TA is described in ClinVar as [Benign]. Clinvar id is 1206384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.779-12dupT		intron_variant		ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.779-12dupT		intron_variant		1	NM_138694.4	ENSP00000360158.3
PKHD1	ENST00000340994.4	c.779-12dupT		intron_variant		5		ENSP00000341097.4

Frequencies

GnomAD3 genomes AF: 0.691 AC: 99469 AN: 143940 Hom.: 35028 Cov.: 0

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.730

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.717

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.444 AC: 358782 AN: 807850 Hom.: 4297 Cov.: 13 AF XY: 0.445 AC XY: 188844 AN XY: 424266

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.691 AC: 99450 AN: 143972 Hom.: 35007 Cov.: 0 AF XY: 0.693 AC XY: 48296 AN XY: 69694

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.714

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Polycystic kidney disease 4 Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Mar 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Autosomal recessive polycystic kidney disease Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

May 15, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs5876252; hg19: chr6-51930886;