chr19-40014607-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178544.5(ZNF546):c.1337G>A(p.Cys446Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,308 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
4
7
2
Clinical Significance
Conservation
PhyloP100: 5.46
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]
Genome browser will be placed here
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.1337G>A | p.Cys446Tyr | missense_variant | 7/7 | ENST00000347077.9 | |
ZNF546 | NM_001297763.2 | c.1259G>A | p.Cys420Tyr | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF546 | ENST00000347077.9 | c.1337G>A | p.Cys446Tyr | missense_variant | 7/7 | 1 | NM_178544.5 | P2 | |
ZNF546 | ENST00000600094.5 | c.1259G>A | p.Cys420Tyr | missense_variant | 7/7 | 2 | A2 | ||
ZNF546 | ENST00000596894.5 | c.77-1821G>A | intron_variant | 3 | |||||
ZNF546 | ENST00000651981.1 | c.*1291G>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: 1461308Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 726960
GnomAD4 exome
AF:
AC:
1
AN:
1461308
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
726960
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
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 | Dec 21, 2023 | The c.1337G>A (p.C446Y) 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 1337, causing the cysteine (C) at amino acid position 446 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
Uncertain
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
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.67
.;Gain of MoRF binding (P = 0.0769);
MVP
MPC
0.45
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