6-51616527-ATTT-AT

Variant names:

• chr6-51616527-ATT-A
• rs113144792
• NM_138694.4:c.*2552_*2553delAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_138694.4(PKHD1):​c.*2552_*2553delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 352,432 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 0.00018 (0 hom., cov: 28)
  • Exomes 𝑓: 0.018 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0183 (3858/211220) while in subpopulation AFR AF= 0.0226 (140/6192). AF 95% confidence interval is 0.0196. There are 0 homozygotes in gnomad4_exome. There are 1935 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.*2552_*2553delAA		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.*2552_*2553delAA		3_prime_UTR_variant	Exon 67 of 67	1	NM_138694.4	ENSP00000360158.3
ENSG00000228689	ENST00000454361.1	n.81-5814_81-5813delTT		intron_variant	Intron 1 of 1	3
ENSG00000228689	ENST00000589278.6	n.811-5819_811-5818delTT		intron_variant	Intron 2 of 2	5
ENSG00000228689	ENST00000650088.1	n.222-5814_222-5813delTT		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.000156 AC: 22 AN: 141164 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000104

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: 0.00103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000109

Gnomad OTH AF: 0.00105

GnomAD4 exome AF: 0.0183 AC: 3858 AN: 211220 Hom.: 0 AF XY: 0.0180 AC XY: 1935 AN XY: 107390

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0159

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.0198

Gnomad4 FIN exome AF: 0.0180

Gnomad4 NFE exome AF: 0.0188

Gnomad4 OTH exome AF: 0.0165

GnomAD4 genome AF: 0.000177 AC: 25 AN: 141212 Hom.: 0 Cov.: 28 AF XY: 0.000219 AC XY: 15 AN XY: 68388

Gnomad4 AFR AF: 0.000182

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.000109

Gnomad4 OTH AF: 0.00104

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;