chr5-141945432-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_016580.4(PCDH12):c.3504G>A(p.Thr1168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,605,174 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 (★).
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
PCDH12
NM_016580.4 synonymous
NM_016580.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.219
Genes affected
PCDH12 (HGNC:8657): (protocadherin 12) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 5-141945432-C-T is Benign according to our data. Variant chr5-141945432-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1641108.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.219 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH12 | NM_016580.4 | c.3504G>A | p.Thr1168= | synonymous_variant | 4/4 | ENST00000231484.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH12 | ENST00000231484.4 | c.3504G>A | p.Thr1168= | synonymous_variant | 4/4 | 1 | NM_016580.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000398 AC: 6AN: 150698Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000445 AC: 11AN: 247294Hom.: 0 AF XY: 0.0000448 AC XY: 6AN XY: 134040
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1454476Hom.: 0 Cov.: 66 AF XY: 0.0000180 AC XY: 13AN XY: 723370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at