19-2933701-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_021217.3(ZNF77):c.1426G>A(p.Ala476Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,611,104 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A476D) has been classified as Uncertain significance.
Frequency
Consequence
NM_021217.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF77 | NM_021217.3 | c.1426G>A | p.Ala476Thr | missense_variant | 4/4 | ENST00000314531.5 | |
ZNF77 | XM_047439170.1 | c.1330G>A | p.Ala444Thr | missense_variant | 4/4 | ||
ZNF77 | XM_017027081.2 | c.886G>A | p.Ala296Thr | missense_variant | 3/3 | ||
ZNF77 | XM_047439171.1 | c.886G>A | p.Ala296Thr | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF77 | ENST00000314531.5 | c.1426G>A | p.Ala476Thr | missense_variant | 4/4 | 1 | NM_021217.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152114Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250012Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135052
GnomAD4 exome AF: 0.0000452 AC: 66AN: 1458990Hom.: 3 Cov.: 78 AF XY: 0.0000455 AC XY: 33AN XY: 725308
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152114Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74286
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2021 | The c.1426G>A (p.A476T) alteration is located in exon 4 (coding exon 4) of the ZNF77 gene. This alteration results from a G to A substitution at nucleotide position 1426, causing the alanine (A) at amino acid position 476 to be replaced by a threonine (T). 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