chr6-109465867-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_014797.3(ZBTB24):c.2078G>A(p.Gly693Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,614,198 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 (★★).
Frequency
Consequence
NM_014797.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZBTB24 | NM_014797.3 | c.2078G>A | p.Gly693Asp | missense_variant | 7/7 | ENST00000230122.4 | NP_055612.2 | |
MICAL1 | NM_001286613.2 | c.-190G>A | 5_prime_UTR_variant | 1/25 | NP_001273542.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZBTB24 | ENST00000230122.4 | c.2078G>A | p.Gly693Asp | missense_variant | 7/7 | 1 | NM_014797.3 | ENSP00000230122 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251482Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135920
GnomAD4 exome AF: 0.000250 AC: 365AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.000248 AC XY: 180AN XY: 727238
GnomAD4 genome AF: 0.000158 AC: 24AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74484
ClinVar
Submissions by phenotype
Immunodeficiency-centromeric instability-facial anomalies syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 693 of the ZBTB24 protein (p.Gly693Asp). This variant is present in population databases (rs146770659, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ZBTB24-related conditions. ClinVar contains an entry for this variant (Variation ID: 839315). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 20, 2023 | The c.2078G>A (p.G693D) alteration is located in exon 7 (coding exon 6) of the ZBTB24 gene. This alteration results from a G to A substitution at nucleotide position 2078, causing the glycine (G) at amino acid position 693 to be replaced by an aspartic acid (D). 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