chr7-47846960-C-G
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PP3_StrongPP5
The NM_138295.5(PKD1L1):c.5072G>C(p.Cys1691Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_138295.5 missense
Scores
Clinical Significance
Conservation
Publications
- heterotaxy, visceral, 8, autosomalInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
- situs inversusInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKD1L1 | ENST00000289672.7 | c.5072G>C | p.Cys1691Ser | missense_variant | Exon 32 of 57 | 1 | NM_138295.5 | ENSP00000289672.2 | ||
PKD1L1 | ENST00000690269.1 | c.5072G>C | p.Cys1691Ser | missense_variant | Exon 32 of 58 | ENSP00000510743.1 | ||||
PKD1L1 | ENST00000685709.1 | c.4904G>C | p.Cys1635Ser | missense_variant | Exon 31 of 56 | ENSP00000509540.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33 show subpopulations
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727122 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74382 show subpopulations
ClinVar
Submissions by phenotype
Situs inversus Pathogenic:1
Pathogenicity based on finding the variant in the homozygous state in a female with situs inversus totalis and congenital heart defect. -
Heterotaxy, visceral, 8, autosomal Pathogenic:1
- -
Inborn genetic diseases Uncertain:1
The c.5072G>C (p.C1691S) alteration is located in exon 32 (coding exon 32) of the PKD1L1 gene. This alteration results from a G to C substitution at nucleotide position 5072, causing the cysteine (C) at amino acid position 1691 to be replaced by a serine (S). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been identified in the homozygous state and/or in conjunction with other PKD1L1 variant(s) in individual(s) with features consistent with PKD1L1-related visceral heterotaxy (Vetrini, 2016). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at