chr16-31061303-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024706.5(ZNF668):c.1625G>A(p.Arg542Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,424,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
ZNF668
NM_024706.5 missense
NM_024706.5 missense
Scores
2
8
6
Clinical Significance
Conservation
PhyloP100: 1.22
Genes affected
ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator 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 |
---|---|---|---|---|---|---|---|
ZNF668 | NM_024706.5 | c.1625G>A | p.Arg542Gln | missense_variant | 3/3 | ENST00000300849.5 | |
ZNF668 | NM_001172669.2 | c.1694G>A | p.Arg565Gln | missense_variant | 4/4 | ||
ZNF668 | NM_001172668.2 | c.1625G>A | p.Arg542Gln | missense_variant | 3/3 | ||
ZNF668 | NM_001172670.2 | c.1625G>A | p.Arg542Gln | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF668 | ENST00000300849.5 | c.1625G>A | p.Arg542Gln | missense_variant | 3/3 | 1 | NM_024706.5 | P1 | |
ENST00000622229.1 | n.1880C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000455 AC: 1AN: 219850Hom.: 0 AF XY: 0.00000854 AC XY: 1AN XY: 117038
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GnomAD4 exome AF: 0.00000351 AC: 5AN: 1424788Hom.: 0 Cov.: 30 AF XY: 0.00000426 AC XY: 3AN XY: 704320
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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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 | Oct 25, 2023 | The c.1694G>A (p.R565Q) alteration is located in exon 4 (coding exon 3) of the ZNF668 gene. This alteration results from a G to A substitution at nucleotide position 1694, causing the arginine (R) at amino acid position 565 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Vest4
MutPred
Loss of sheet (P = 0.1907);.;Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;
MVP
MPC
2.0
ClinPred
D
GERP RS
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