chr19-47066656-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_015168.2(ZC3H4):c.3612C>T(p.Ala1204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,611,784 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00076 ( 12 hom. )
Consequence
ZC3H4
NM_015168.2 synonymous
NM_015168.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.88
Genes affected
ZC3H4 (HGNC:17808): (zinc finger CCCH-type containing 4) This gene encodes a member of a family of CCCH (C-x8-C-x5-C-x3-H type) zinc finger domain-containing proteins. These zinc finger domains, which coordinate zinc finger binding and are characterized by three cysteine residues and one histidine residue, are nucleic acid-binding. Other family members are known to function in post-transcriptional regulation. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 19-47066656-G-A is Benign according to our data. Variant chr19-47066656-G-A is described in ClinVar as [Benign]. Clinvar id is 3034160.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.88 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000757 (1105/1459428) while in subpopulation AMR AF= 0.022 (980/44590). AF 95% confidence interval is 0.0208. There are 12 homozygotes in gnomad4_exome. There are 465 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 165 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZC3H4 | NM_015168.2 | c.3612C>T | p.Ala1204= | synonymous_variant | 15/15 | ENST00000253048.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZC3H4 | ENST00000253048.10 | c.3612C>T | p.Ala1204= | synonymous_variant | 15/15 | 1 | NM_015168.2 | P1 | |
ZC3H4 | ENST00000601973.1 | c.2433C>T | p.Ala811= | synonymous_variant | 8/8 | 5 | |||
ZC3H4 | ENST00000594019.5 | n.1462C>T | non_coding_transcript_exon_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 162AN: 152238Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00366 AC: 875AN: 239078Hom.: 11 AF XY: 0.00277 AC XY: 363AN XY: 131154
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GnomAD4 exome AF: 0.000757 AC: 1105AN: 1459428Hom.: 12 Cov.: 33 AF XY: 0.000641 AC XY: 465AN XY: 725944
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GnomAD4 genome AF: 0.00108 AC: 165AN: 152356Hom.: 3 Cov.: 33 AF XY: 0.00103 AC XY: 77AN XY: 74500
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ZC3H4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 24, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at