chr19-40014598-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178544.5(ZNF546):c.1328G>A(p.Cys443Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,312 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: 6.8e-7 ( 0 hom. )
Consequence
ZNF546
NM_178544.5 missense
NM_178544.5 missense
Scores
6
5
2
Clinical Significance
Conservation
PhyloP100: 6.63
Genes affected
ZNF546 (HGNC:28671): (zinc finger protein 546) 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 integral component of membrane. 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 |
---|---|---|---|---|---|---|---|
ZNF546 | NM_178544.5 | c.1328G>A | p.Cys443Tyr | missense_variant | 7/7 | ENST00000347077.9 | |
ZNF546 | NM_001297763.2 | c.1250G>A | p.Cys417Tyr | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF546 | ENST00000347077.9 | c.1328G>A | p.Cys443Tyr | missense_variant | 7/7 | 1 | NM_178544.5 | P2 | |
ZNF546 | ENST00000600094.5 | c.1250G>A | p.Cys417Tyr | missense_variant | 7/7 | 2 | A2 | ||
ZNF546 | ENST00000596894.5 | c.77-1830G>A | intron_variant | 3 | |||||
ZNF546 | ENST00000651981.1 | c.*1282G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461312Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 726956
GnomAD4 exome
AF:
AC:
1
AN:
1461312
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
726956
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 19, 2024 | The c.1328G>A (p.C443Y) alteration is located in exon 7 (coding exon 5) of the ZNF546 gene. This alteration results from a G to A substitution at nucleotide position 1328, causing the cysteine (C) at amino acid position 443 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.69
.;Gain of phosphorylation at C443 (P = 0.0643);
MVP
MPC
0.55
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.