chr19-8512481-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001146175.2(ZNF414):c.436C>T(p.Arg146Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
ZNF414
NM_001146175.2 missense
NM_001146175.2 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 4.04
Genes affected
ZNF414 (HGNC:20630): (zinc finger protein 414) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF414 | NM_001146175.2 | c.436C>T | p.Arg146Cys | missense_variant | 4/8 | ENST00000393927.9 | |
ZNF414 | NM_032370.3 | c.436C>T | p.Arg146Cys | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF414 | ENST00000393927.9 | c.436C>T | p.Arg146Cys | missense_variant | 4/8 | 1 | NM_001146175.2 | P1 | |
ZNF414 | ENST00000255616.8 | c.436C>T | p.Arg146Cys | missense_variant | 4/6 | 1 | |||
ZNF414 | ENST00000599379.1 | c.123C>T | p.Ser41= | synonymous_variant, NMD_transcript_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251062Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135744
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461808Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727204
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74298
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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 | Mar 02, 2023 | The c.436C>T (p.R146C) alteration is located in exon 4 (coding exon 4) of the ZNF414 gene. This alteration results from a C to T substitution at nucleotide position 436, causing the arginine (R) at amino acid position 146 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
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
1.0
.;D
Vest4
MutPred
Loss of disorder (P = 0.0806);Loss of disorder (P = 0.0806);
MVP
MPC
ClinPred
D
GERP RS
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