rs775831255
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_138694.4(PKHD1):c.6996G>A(p.Glu2332=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000000686 in 1,457,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PKHD1
NM_138694.4 splice_region, synonymous
NM_138694.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.9995
2
Clinical Significance
Conservation
PhyloP100: 4.43
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKHD1 | NM_138694.4 | c.6996G>A | p.Glu2332= | splice_region_variant, synonymous_variant | 43/67 | ENST00000371117.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.6996G>A | p.Glu2332= | splice_region_variant, synonymous_variant | 43/67 | 1 | NM_138694.4 | P2 | |
PKHD1 | ENST00000340994.4 | c.6996G>A | p.Glu2332= | splice_region_variant, synonymous_variant | 43/61 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457570Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 725252
GnomAD4 exome
AF:
AC:
1
AN:
1457570
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
725252
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive polycystic kidney disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2015 | In summary, this is a novel silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of silent changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has not been published in the literature and is not present in population databases. This sequence change affects codon 2332 of the PKHD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PKHD1 protein. It also falls at the last nucleotide of exon 43 of the PKHD1 mRNA. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at