chr19-40014637-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_178544.5(ZNF546):c.1367T>C(p.Leu456Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L456V) has been classified as Uncertain significance.
Frequency
Consequence
NM_178544.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF546 | NM_178544.5 | c.1367T>C | p.Leu456Pro | missense_variant | 7/7 | ENST00000347077.9 | |
ZNF546 | NM_001297763.2 | c.1289T>C | p.Leu430Pro | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF546 | ENST00000347077.9 | c.1367T>C | p.Leu456Pro | missense_variant | 7/7 | 1 | NM_178544.5 | P2 | |
ZNF546 | ENST00000600094.5 | c.1289T>C | p.Leu430Pro | missense_variant | 7/7 | 2 | A2 | ||
ZNF546 | ENST00000596894.5 | c.77-1791T>C | intron_variant | 3 | |||||
ZNF546 | ENST00000651981.1 | c.*1321T>C | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2023 | The c.1367T>C (p.L456P) alteration is located in exon 7 (coding exon 5) of the ZNF546 gene. This alteration results from a T to C substitution at nucleotide position 1367, causing the leucine (L) at amino acid position 456 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.