chr6-51616527-A-ATTTT

Variant names:

• chr6-51616527-A-ATTTT
• rs113144792
• NM_138694.4:c.*2550_*2553dupAAAA

Variant summary

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

The NM_138694.4(PKHD1):​c.*2550_*2553dupAAAA variant causes a 3 prime UTR 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 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000091 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKHD1 NM_138694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 0 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: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Caroli disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000228689 (HGNC:):

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	NM_138694.4	MANE Select	c.*2550_*2553dupAAAA		3_prime_UTR	Exon 67 of 67	NP_619639.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	ENST00000371117.8	TSL:1 MANE Select	c.*2550_*2553dupAAAA		3_prime_UTR	Exon 67 of 67	ENSP00000360158.3	P08F94-1
	ENSG00000228689	ENST00000454361.1	TSL:3	n.81-5816_81-5813dupTTTT		intron	N/A
	ENSG00000228689	ENST00000589278.6	TSL:5	n.811-5821_811-5818dupTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141240 Hom.: 0 Cov.: 28

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000910 AC: 2 AN: 219856 Hom.: 0 Cov.: 0 AF XY: 0.0000179 AC XY: 2 AN XY: 111788

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

African (AFR) AF: 0.00 AC: 0 AN: 6450

American (AMR) AF: 0.00 AC: 0 AN: 6706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8252

East Asian (EAS) AF: 0.00 AC: 0 AN: 20998

South Asian (SAS) AF: 0.00 AC: 0 AN: 2064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1130

European-Non Finnish (NFE) AF: 0.0000141 AC: 2 AN: 141504

Other (OTH) AF: 0.00 AC: 0 AN: 14566

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 141240 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 68356

African (AFR) AF: 0.00 AC: 0 AN: 38434

American (AMR) AF: 0.00 AC: 0 AN: 14014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3300

East Asian (EAS) AF: 0.00 AC: 0 AN: 4886

South Asian (SAS) AF: 0.00 AC: 0 AN: 4344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64440

Other (OTH) AF: 0.00 AC: 0 AN: 1910

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.079

Splicing

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

Other links and lift over

dbSNP: rs113144792; hg19: chr6-51481325;