12-8177140-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001004328.3(ZNF705A):c.460C>T(p.Arg154Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R154H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001004328.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF705A | ENST00000396570.8 | c.460C>T | p.Arg154Cys | missense_variant | Exon 6 of 6 | 5 | NM_001004328.3 | ENSP00000379816.4 | ||
ZNF705A | ENST00000359286.4 | c.460C>T | p.Arg154Cys | missense_variant | Exon 5 of 5 | 2 | ENSP00000352233.4 | |||
ZNF705A | ENST00000610508.4 | c.460C>T | p.Arg154Cys | missense_variant | Exon 6 of 6 | 5 | ENSP00000481663.1 | |||
ZNF705A | ENST00000398526.2 | c.226C>T | p.Arg76Cys | missense_variant | Exon 2 of 3 | 3 | ENSP00000475525.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251112Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135714
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1459662Hom.: 0 Cov.: 102 AF XY: 0.0000275 AC XY: 20AN XY: 726128
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.460C>T (p.R154C) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a C to T substitution at nucleotide position 460, causing the arginine (R) at amino acid position 154 to be replaced by a cysteine (C). 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