16-87411786-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_015144.3(ZCCHC14):c.2935G>A(p.Gly979Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,611,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
ZCCHC14
NM_015144.3 missense
NM_015144.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 0.888
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.050162315).
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZCCHC14 | NM_015144.3 | c.2935G>A | p.Gly979Ser | missense_variant | 12/13 | ENST00000671377.2 | |
ZCCHC14 | XM_005255858.4 | c.2935G>A | p.Gly979Ser | missense_variant | 12/12 | ||
ZCCHC14 | XM_017023082.3 | c.2416G>A | p.Gly806Ser | missense_variant | 12/12 | ||
ZCCHC14 | XR_243401.4 | n.3721G>A | non_coding_transcript_exon_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZCCHC14 | ENST00000671377.2 | c.2935G>A | p.Gly979Ser | missense_variant | 12/13 | NM_015144.3 | P1 | ||
ZCCHC14 | ENST00000268616.9 | c.2524G>A | p.Gly842Ser | missense_variant | 12/13 | 1 | |||
ZCCHC14 | ENST00000568020.6 | c.2557G>A | p.Gly853Ser | missense_variant, NMD_transcript_variant | 12/14 | 1 | |||
ZCCHC14 | ENST00000561928.1 | c.2176G>A | p.Gly726Ser | missense_variant | 10/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152224Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000570 AC: 14AN: 245638Hom.: 0 AF XY: 0.0000674 AC XY: 9AN XY: 133528
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GnomAD4 exome AF: 0.000158 AC: 230AN: 1459164Hom.: 1 Cov.: 95 AF XY: 0.000149 AC XY: 108AN XY: 725914
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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ExAC
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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 | Dec 26, 2023 | The c.2524G>A (p.G842S) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a G to A substitution at nucleotide position 2524, causing the glycine (G) at amino acid position 842 to be replaced by a serine (S). 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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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