chr16-2110250-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001009944.3(PKD1):c.4917C>T(p.Gly1639=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,611,986 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G1639G) has been classified as Likely benign.
Frequency
Consequence
NM_001009944.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.4917C>T | p.Gly1639= | synonymous_variant | 15/46 | ENST00000262304.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.4917C>T | p.Gly1639= | synonymous_variant | 15/46 | 1 | NM_001009944.3 | P5 |
Frequencies
GnomAD3 genomes AF: 0.00154 AC: 235AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00137 AC: 335AN: 244598Hom.: 0 AF XY: 0.00129 AC XY: 173AN XY: 133708
GnomAD4 exome AF: 0.00193 AC: 2824AN: 1459636Hom.: 6 Cov.: 36 AF XY: 0.00190 AC XY: 1381AN XY: 726094
GnomAD4 genome AF: 0.00154 AC: 235AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.00142 AC XY: 106AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 29, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | PKD1: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 01, 2021 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Polycystic kidney disease, adult type Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 27, 2020 | - - |
Polycystic kidney disease Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The PKD1 p.Gly1639= variant was not identified in the literature nor was it identified in the databases GeneInsight-COGR or PKD1-LOVD. The variant was identified in dbSNP (ID: rs148852027) as "With Likely benign allele", ClinVar (2x, likely benign), Clinvitae, LOVD 3.0 (1x), and the ADPKD Mutation Database (likely neutral). The variant was identified in control databases in 387 of 271600 chromosomes at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 7 of 23132 chromosomes (freq: 0.0003), Other in 11 of 6314 chromosomes (freq: 0.002), Latino in 53 of 34320 chromosomes (freq: 0.002), European in 298 of 123000 chromosomes (freq: 0.002), Ashkenazi Jewish in 3 of 10006 chromosomes (freq: 0.0003), Finnish in 5 of 25308 chromosomes (freq: 0.0002), and South Asian in 10 of 30744 chromosomes (freq: 0.0003). The variant was not observed in the East Asian population. In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.Gly1639= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at