chr16-67662493-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001037281.2(PARD6A):āc.884A>Gā(p.Asn295Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,613,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 33)
Exomes š: 0.00016 ( 0 hom. )
Consequence
PARD6A
NM_001037281.2 missense
NM_001037281.2 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 4.28
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.15428627).
BS2
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARD6A | NM_001037281.2 | c.884A>G | p.Asn295Ser | missense_variant | 3/3 | ENST00000458121.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARD6A | ENST00000458121.7 | c.884A>G | p.Asn295Ser | missense_variant | 3/3 | 1 | NM_001037281.2 | A1 | |
PARD6A | ENST00000219255.3 | c.887A>G | p.Asn296Ser | missense_variant | 3/3 | 1 | P4 | ||
PARD6A | ENST00000602551.5 | c.797A>G | p.Asn266Ser | missense_variant | 3/3 | 5 | |||
PARD6A | ENST00000602727.1 | n.1044A>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152162Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000997 AC: 25AN: 250636Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135694
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GnomAD4 exome AF: 0.000157 AC: 230AN: 1461272Hom.: 0 Cov.: 32 AF XY: 0.000155 AC XY: 113AN XY: 726942
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2023 | The c.887A>G (p.N296S) alteration is located in exon 3 (coding exon 3) of the PARD6A gene. This alteration results from a A to G substitution at nucleotide position 887, causing the asparagine (N) at amino acid position 296 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Sift4G
Benign
T;T;T
Polyphen
0.98, 0.97
.;D;D
Vest4
MVP
MPC
0.43
ClinPred
T
GERP RS
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gMVP
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