6-52066088-TAAA-TAAAAA

Position:

• chr6-52066088-TAAA-TAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_138694.4(PKHD1):​c.779-13_779-12dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 0)
  • Exomes 𝑓: 0.022 (1 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0216 (17413/807862) while in subpopulation AMR AF= 0.0282 (1078/38204). AF 95% confidence interval is 0.0268. There are 1 homozygotes in gnomad4_exome. There are 8654 alleles in male gnomad4_exome subpopulation. Median coverage is 13. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.779-13_779-12dupTT		intron_variant		ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.779-13_779-12dupTT		intron_variant		1	NM_138694.4	ENSP00000360158.3
PKHD1	ENST00000340994.4	c.779-13_779-12dupTT		intron_variant		5		ENSP00000341097.4

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 260 AN: 144014 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00264

Gnomad EAS AF: 0.00199

Gnomad SAS AF: 0.000882

Gnomad FIN AF: 0.00318

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000801

Gnomad OTH AF: 0.00254

GnomAD4 exome AF: 0.0216 AC: 17413 AN: 807862 Hom.: 1 Cov.: 13 AF XY: 0.0204 AC XY: 8654 AN XY: 424464

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.0282

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0228

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.00181 AC: 261 AN: 144046 Hom.: 1 Cov.: 0 AF XY: 0.00201 AC XY: 140 AN XY: 69714

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.00264

Gnomad4 EAS AF: 0.00200

Gnomad4 SAS AF: 0.000887

Gnomad4 FIN AF: 0.00318

Gnomad4 NFE AF: 0.000801

Gnomad4 OTH AF: 0.00252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;