6-51616527-ATTT-ATT

Variant names:

• chr6-51616527-AT-A
• rs113144792
• NM_138694.4:c.*2553delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_138694.4(PKHD1):​c.*2553delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 348,952 control chromosomes in the GnomAD database, including 44 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (42 hom., cov: 28)
  • Exomes 𝑓: 0.30 (2 hom.)
• Consequence: PKHD1 NM_138694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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]

ENSG00000228689 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.*2553delA		3_prime_UTR_variant	Exon 67 of 67	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117	c.*2553delA		3_prime_UTR_variant	Exon 67 of 67	1	NM_138694.4	ENSP00000360158.3
ENSG00000228689	ENST00000454361.1	n.81-5813delT		intron_variant	Intron 1 of 1	3
ENSG00000228689	ENST00000589278.6	n.811-5818delT		intron_variant	Intron 2 of 2	5
ENSG00000228689	ENST00000650088.1	n.222-5813delT		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 2807 AN: 140834 Hom.: 41 Cov.: 28

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00455

Gnomad EAS AF: 0.00841

Gnomad SAS AF: 0.00554

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0233

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0142

GnomAD4 exome AF: 0.304 AC: 63257 AN: 208072 Hom.: 2 Cov.: 0 AF XY: 0.305 AC XY: 32212 AN XY: 105526

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.0200 AC: 2818 AN: 140880 Hom.: 42 Cov.: 28 AF XY: 0.0209 AC XY: 1425 AN XY: 68210

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00455

Gnomad4 EAS AF: 0.00843

Gnomad4 SAS AF: 0.00533

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.00591

Gnomad4 OTH AF: 0.0146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs113144792; hg19: chr6-51481325;