16-67662154-C-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001037281.2(PARD6A):āc.545C>Gā(p.Pro182Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0016 ( 0 hom., cov: 33)
Exomes š: 0.00014 ( 0 hom. )
Consequence
PARD6A
NM_001037281.2 missense
NM_001037281.2 missense
Scores
4
3
7
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
PARD6A (HGNC:15943): (par-6 family cell polarity regulator alpha) This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009187371).
BP6
Variant 16-67662154-C-G is Benign according to our data. Variant chr16-67662154-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3051049.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 249 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARD6A | NM_001037281.2 | c.545C>G | p.Pro182Arg | missense_variant | 3/3 | ENST00000458121.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARD6A | ENST00000458121.7 | c.545C>G | p.Pro182Arg | missense_variant | 3/3 | 1 | NM_001037281.2 | A1 | |
PARD6A | ENST00000219255.3 | c.548C>G | p.Pro183Arg | missense_variant | 3/3 | 1 | P4 | ||
PARD6A | ENST00000602551.5 | c.458C>G | p.Pro153Arg | missense_variant | 3/3 | 5 | |||
PARD6A | ENST00000602727.1 | n.705C>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00164 AC: 249AN: 152138Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000398 AC: 100AN: 251220Hom.: 0 AF XY: 0.000309 AC XY: 42AN XY: 135830
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GnomAD4 exome AF: 0.000138 AC: 202AN: 1461674Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77AN XY: 727134
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GnomAD4 genome AF: 0.00164 AC: 249AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.00153 AC XY: 114AN XY: 74446
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PARD6A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 28, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D
Polyphen
1.0, 0.99
.;D;D
Vest4
MVP
MPC
1.1
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at