19-53165111-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024733.5(ZNF665):c.1379G>A(p.Cys460Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
ZNF665
NM_024733.5 missense
NM_024733.5 missense
Scores
4
6
7
Clinical Significance
Conservation
PhyloP100: 5.07
Genes affected
ZNF665 (HGNC:25885): (zinc finger protein 665) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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 |
---|---|---|---|---|---|---|---|
ZNF665 | NM_024733.5 | c.1379G>A | p.Cys460Tyr | missense_variant | 4/4 | ENST00000396424.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF665 | ENST00000396424.5 | c.1379G>A | p.Cys460Tyr | missense_variant | 4/4 | 2 | NM_024733.5 | P1 | |
ZNF665 | ENST00000650736.1 | c.1379G>A | p.Cys460Tyr | missense_variant | 5/5 | P1 | |||
ZNF665 | ENST00000600412.1 | c.1184G>A | p.Cys395Tyr | missense_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461878Hom.: 0 Cov.: 81 AF XY: 0.00000963 AC XY: 7AN XY: 727236
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74250
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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 | Jan 17, 2024 | The c.1379G>A (p.C460Y) alteration is located in exon 4 (coding exon 3) of the ZNF665 gene. This alteration results from a G to A substitution at nucleotide position 1379, causing the cysteine (C) at amino acid position 460 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
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of ubiquitination at K465 (P = 0.0624);.;
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