12-71611075-G-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_144982.5(ZFC3H1):āc.5752C>Gā(p.Leu1918Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,465,912 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 (ā ).
Frequency
Genomes: š 0.00010 ( 0 hom., cov: 30)
Exomes š: 0.0000037 ( 0 hom. )
Consequence
ZFC3H1
NM_144982.5 missense
NM_144982.5 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
ZFC3H1 (HGNC:28328): (zinc finger C3H1-type containing) Predicted to enable metal ion binding activity. Predicted to be involved in RNA processing. Located in nucleus. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.09667137).
BS2
High AC in GnomAd4 at 12 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFC3H1 | NM_144982.5 | c.5752C>G | p.Leu1918Val | missense_variant | 33/35 | ENST00000378743.9 | |
ZFC3H1 | XM_047428485.1 | c.4573C>G | p.Leu1525Val | missense_variant | 33/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFC3H1 | ENST00000378743.9 | c.5752C>G | p.Leu1918Val | missense_variant | 33/35 | 1 | NM_144982.5 | P1 | |
ZFC3H1 | ENST00000552994.5 | c.*707C>G | 3_prime_UTR_variant, NMD_transcript_variant | 32/34 | 1 | ||||
ZFC3H1 | ENST00000547398.1 | n.212C>G | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
ZFC3H1 | ENST00000550963.1 | n.180C>G | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000104 AC: 12AN: 115814Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.00000370 AC: 5AN: 1350040Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1AN XY: 670220
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GnomAD4 genome AF: 0.000104 AC: 12AN: 115872Hom.: 0 Cov.: 30 AF XY: 0.0000915 AC XY: 5AN XY: 54648
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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 | Jun 03, 2022 | The c.5752C>G (p.L1918V) alteration is located in exon 33 (coding exon 33) of the ZFC3H1 gene. This alteration results from a C to G substitution at nucleotide position 5752, causing the leucine (L) at amino acid position 1918 to be replaced by a valine (V). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at I1916 (P = 0.0103);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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