NM_138694.4:c.779-17_779-12dupTTTTTT

Variant names:

• chr6-52066088-T-TAAAAAA
• rs5876252
• NM_138694.4:c.779-17_779-12dupTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138694.4(PKHD1):​c.779-17_779-12dupTTTTTT 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 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive polycystic kidney disease

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
• polycystic kidney disease 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Genomics England PanelApp
• Caroli disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	NM_138694.4	MANE Select	c.779-17_779-12dupTTTTTT		intron	N/A	NP_619639.3
	PKHD1	NM_170724.3		c.779-17_779-12dupTTTTTT		intron	N/A	NP_733842.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	ENST00000371117.8	TSL:1 MANE Select	c.779-12_779-11insTTTTTT		intron	N/A	ENSP00000360158.3
	PKHD1	ENST00000340994.4	TSL:5	c.779-12_779-11insTTTTTT		intron	N/A	ENSP00000341097.4

Frequencies

GnomAD3 genomes AF: 0.00000694 AC: 1 AN: 144044 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 815338 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 428432

African (AFR) AF: 0.00 AC: 0 AN: 21158

American (AMR) AF: 0.00 AC: 0 AN: 38640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21064

East Asian (EAS) AF: 0.00 AC: 0 AN: 33812

South Asian (SAS) AF: 0.00 AC: 0 AN: 67694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 548494

Other (OTH) AF: 0.00 AC: 0 AN: 38242

GnomAD4 genome AF: 0.00000694 AC: 1 AN: 144044 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 69684

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39100

American (AMR) AF: 0.00 AC: 0 AN: 14462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 5020

South Asian (SAS) AF: 0.00 AC: 0 AN: 4536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66174

Other (OTH) AF: 0.00 AC: 0 AN: 1970

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5876252; hg19: chr6-51930886;