rs113144792

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-51616527-ATTTT-A
• chr6-51616527-ATTTT-AT
• chr6-51616527-ATTTT-ATT
• chr6-51616527-ATTTT-ATTT
• chr6-51616527-ATTTT-ATTTTT
• chr6-51616527-ATTTT-ATTTTTT
• chr6-51616527-ATTTT-ATTTTTTT
• chr6-51616527-ATTTT-ATTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138694.4(PKHD1):​c.*2550_*2553delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 219,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKHD1 NM_138694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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_*2553delAAAA		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_*2553delAAAA		3_prime_UTR	Exon 67 of 67	ENSP00000360158.3	P08F94-1
	ENSG00000228689	ENST00000454361.1	TSL:3	n.81-5816_81-5813delTTTT		intron	N/A
	ENSG00000228689	ENST00000589278.6	TSL:5	n.811-5821_811-5818delTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141234 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: 0.0000364 AC: 8 AN: 219780 Hom.: 0 AF XY: 0.0000358 AC XY: 4 AN XY: 111752

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

African (AFR) AF: 0.000155 AC: 1 AN: 6444

American (AMR) AF: 0.00 AC: 0 AN: 6710

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 20996

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

European-Finnish (FIN) AF: 0.000110 AC: 2 AN: 18180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1128

European-Non Finnish (NFE) AF: 0.0000283 AC: 4 AN: 141446

Other (OTH) AF: 0.0000687 AC: 1 AN: 14560

⚠️ 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: 141234 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: 8726

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: 1908

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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

Other links and lift over

dbSNP: rs113144792; hg19: chr6-51481325;