rs200279871
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The NM_001903.5(CTNNA1):āc.1593A>Gā(p.Gln531=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,172 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000043 ( 0 hom. )
Consequence
CTNNA1
NM_001903.5 synonymous
NM_001903.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.419
Genes affected
CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 5-138924556-A-G is Benign according to our data. Variant chr5-138924556-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 239059.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS2
?
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNA1 | NM_001903.5 | c.1593A>G | p.Gln531= | synonymous_variant | 12/18 | ENST00000302763.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNA1 | ENST00000302763.12 | c.1593A>G | p.Gln531= | synonymous_variant | 12/18 | 1 | NM_001903.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000111 AC: 28AN: 251468Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135910
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727246
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74468
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2022 | In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at