chr12-122473531-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_017612.5(ZCCHC8):c.2090G>A(p.Arg697Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017612.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZCCHC8 | ENST00000633063.3 | c.2090G>A | p.Arg697Gln | missense_variant | Exon 14 of 14 | 1 | NM_017612.5 | ENSP00000488055.1 | ||
ZCCHC8 | ENST00000536306.5 | c.1376G>A | p.Arg459Gln | missense_variant | Exon 12 of 12 | 1 | ENSP00000441423.1 | |||
ZCCHC8 | ENST00000543897.5 | c.1376G>A | p.Arg459Gln | missense_variant | Exon 12 of 12 | 1 | ENSP00000438993.1 | |||
ZCCHC8 | ENST00000538116.5 | n.1191G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249130Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135160
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727026
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2090G>A (p.R697Q) alteration is located in exon 14 (coding exon 14) of the ZCCHC8 gene. This alteration results from a G to A substitution at nucleotide position 2090, causing the arginine (R) at amino acid position 697 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 697 of the ZCCHC8 protein (p.Arg697Gln). This variant is present in population databases (rs374767090, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ZCCHC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 2604930). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ZCCHC8 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at