11-110136894-G-A
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033390.2(ZC3H12C):c.253G>A(p.Ala85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033390.2 missense
Scores
Clinical Significance
Conservation
Publications
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive nonsyndromic hearing loss 24Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZC3H12C | ENST00000278590.8 | c.253G>A | p.Ala85Thr | missense_variant | Exon 2 of 6 | 2 | NM_033390.2 | ENSP00000278590.3 | ||
ZC3H12C | ENST00000528673.5 | c.256G>A | p.Ala86Thr | missense_variant | Exon 2 of 6 | 2 | ENSP00000431821.1 | |||
ZC3H12C | ENST00000453089.2 | c.160G>A | p.Ala54Thr | missense_variant | Exon 1 of 5 | 2 | ENSP00000413094.2 | |||
RDX | ENST00000645527.1 | n.*251-5164C>T | intron_variant | Intron 15 of 18 | ENSP00000496121.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 show subpopulations
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461490Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726984 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74330 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.253G>A (p.A85T) alteration is located in exon 2 (coding exon 2) of the ZC3H12C gene. This alteration results from a G to A substitution at nucleotide position 253, causing the alanine (A) at amino acid position 85 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