Genetic Variant PKHD1:c.779-12delT (chr6-52066088-TA-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_138694.4(PKHD1):c.779-12delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0098 ( 29 hom., cov: 0)

Exomes 𝑓: 0.047 ( 0 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.169

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 6-52066088-TA-T is Benign according to our data. Variant chr6-52066088-TA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 357455.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr6-52066088-TA-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.779-12delT		intron_variant	Intron 11 of 66	ENST00000371117.8	NP_619639.3	P08F94-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 link	c.779-12delT		intron_variant	Intron 11 of 66	1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.779-12delT		intron_variant	Intron 11 of 60	5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1408

AN:

143946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00637

Gnomad ASJ

AF:

0.000588

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.000882

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.0127

GnomAD4 exome

AF:

0.0475

AC:

37208

AN:

783414

Hom.:

Cov.:

AF XY:

0.0468

AC XY:

19237

AN XY:

411224

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.0410

Gnomad4 ASJ exome

AF:

0.0427

Gnomad4 EAS exome

AF:

0.0283

Gnomad4 SAS exome

AF:

0.0597

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0461

Gnomad4 OTH exome

AF:

0.0486

GnomAD4 genome

AF:

0.00981

AC:

1412

AN:

143978

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

649

AN XY:

69682

show subpopulations

Gnomad4 AFR

AF:

0.0302

Gnomad4 AMR

AF:

0.00636

Gnomad4 ASJ

AF:

0.000588

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.000887

Gnomad4 FIN

AF:

0.00368

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.0126

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autosomal recessive polycystic kidney disease

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 24, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

6-52066088-TAAAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over