1-37481718-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001323551.2(ZC3H12A):c.-206A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,126 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 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
ZC3H12A
NM_001323551.2 5_prime_UTR_premature_start_codon_gain
NM_001323551.2 5_prime_UTR_premature_start_codon_gain
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: -0.525
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16125995).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZC3H12A | NM_025079.3 | c.701A>G | p.Tyr234Cys | missense_variant | 4/6 | ENST00000373087.7 | NP_079355.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZC3H12A | ENST00000373087.7 | c.701A>G | p.Tyr234Cys | missense_variant | 4/6 | 1 | NM_025079.3 | ENSP00000362179.5 | ||
ZC3H12A | ENST00000471012.1 | c.29A>G | p.Tyr10Cys | missense_variant | 1/2 | 3 | ENSP00000473447.1 | |||
ZC3H12A | ENST00000472312.1 | n.549A>G | non_coding_transcript_exon_variant | 2/2 | 2 | |||||
ZC3H12A | ENST00000640233.1 | n.701A>G | non_coding_transcript_exon_variant | 4/6 | 5 | ENSP00000492053.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
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GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727246
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74368
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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 04, 2022 | The c.701A>G (p.Y234C) alteration is located in exon 4 (coding exon 3) of the ZC3H12A gene. This alteration results from a A to G substitution at nucleotide position 701, causing the tyrosine (Y) at amino acid position 234 to be replaced by a cysteine (C). 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
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Benign
Sift
Benign
D;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
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