13-45963901-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001330564.2(ZC3H13):c.4616G>A(p.Gly1539Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ZC3H13
NM_001330564.2 missense
NM_001330564.2 missense
Scores
9
5
4
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
ZC3H13 (HGNC:20368): (zinc finger CCCH-type containing 13) Enables RNA binding activity. Involved in mRNA methylation. Located in nuclear speck. Part of RNA N6-methyladenosine methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.762
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZC3H13 | NM_001330564.2 | c.4616G>A | p.Gly1539Asp | missense_variant | 17/19 | ENST00000679008.1 | NP_001317493.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZC3H13 | ENST00000679008.1 | c.4616G>A | p.Gly1539Asp | missense_variant | 17/19 | NM_001330564.2 | ENSP00000503994 | A2 | ||
ZC3H13 | ENST00000282007.7 | c.4616G>A | p.Gly1539Asp | missense_variant | 17/17 | 1 | ENSP00000282007 | P2 | ||
ZC3H13 | ENST00000242848.8 | c.4613G>A | p.Gly1538Asp | missense_variant | 17/19 | 5 | ENSP00000242848 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250340Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135450
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461806Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727206
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74454
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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 | Feb 07, 2023 | The c.4616G>A (p.G1539D) alteration is located in exon 17 (coding exon 16) of the ZC3H13 gene. This alteration results from a G to A substitution at nucleotide position 4616, causing the glycine (G) at amino acid position 1539 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0517);.;
MVP
MPC
0.45
ClinPred
D
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