10-62376671-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014951.3(ZNF365):c.478C>T(p.His160Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,854 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
ZNF365
NM_014951.3 missense
NM_014951.3 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 3.58
Genes affected
ZNF365 (HGNC:18194): (zinc finger protein 365) This gene encodes a zinc finger protein that may play a role in the repair of DNA damage and maintenance of genome stability. The N-terminal C2H2 zinc finger motif is required to form a protein complex with PARP1 and MRE11, which are known to be involved in the restart of stalled DNA replication forks. A mutation in this gene may be associated with breast cancer susceptibility. [provided by RefSeq, Mar 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38715565).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF365 | NM_014951.3 | c.478C>T | p.His160Tyr | missense_variant | 2/5 | ENST00000395254.8 | NP_055766.2 | |
ZNF365 | NM_199450.3 | c.478C>T | p.His160Tyr | missense_variant | 2/5 | NP_955522.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF365 | ENST00000395254.8 | c.478C>T | p.His160Tyr | missense_variant | 2/5 | 1 | NM_014951.3 | ENSP00000378674 | P1 | |
ZNF365 | ENST00000395255.7 | c.478C>T | p.His160Tyr | missense_variant | 2/5 | 1 | ENSP00000378675 | |||
ZNF365 | ENST00000466727.1 | n.106+2213C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251466Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135918
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727232
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GnomAD4 genome Cov.: 32
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32
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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 | May 31, 2023 | The c.478C>T (p.H160Y) alteration is located in exon 2 (coding exon 1) of the ZNF365 gene. This alteration results from a C to T substitution at nucleotide position 478, causing the histidine (H) at amino acid position 160 to be replaced by a tyrosine (Y). 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
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of phosphorylation at H160 (P = 0.0298);Gain of phosphorylation at H160 (P = 0.0298);Gain of phosphorylation at H160 (P = 0.0298);
MVP
MPC
0.84
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