chr1-37480319-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_025079.3(ZC3H12A):c.473G>T(p.Arg158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,820 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
ZC3H12A
NM_025079.3 missense
NM_025079.3 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 2.85
Genes affected
ZC3H12A (HGNC:26259): (zinc finger CCCH-type containing 12A) ZC3H12A is an MCP1 (CCL2; MIM 158105)-induced protein that acts as a transcriptional activator and causes cell death of cardiomyocytes, possibly via induction of genes associated with apoptosis.[supplied by OMIM, Mar 2008]
MIR6732 (HGNC:50066): (microRNA 6732) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38176587).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZC3H12A | NM_025079.3 | c.473G>T | p.Arg158Leu | missense_variant | 3/6 | ENST00000373087.7 | |
MIR6732 | NR_106790.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZC3H12A | ENST00000373087.7 | c.473G>T | p.Arg158Leu | missense_variant | 3/6 | 1 | NM_025079.3 | P1 | |
ZC3H12A | ENST00000472312.1 | n.321G>T | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
ZC3H12A | ENST00000640233.1 | c.473G>T | p.Arg158Leu | missense_variant, NMD_transcript_variant | 3/6 | 5 | |||
MIR6732 | ENST00000619365.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 251076Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135714
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461622Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727132
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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 | Oct 13, 2021 | The c.473G>T (p.R158L) alteration is located in exon 3 (coding exon 2) of the ZC3H12A gene. This alteration results from a G to T substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 to be replaced by a leucine (L). 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
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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