2-96761046-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020184.4(CNNM4):c.47G>A(p.Arg16His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,233,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_020184.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNNM4 | NM_020184.4 | c.47G>A | p.Arg16His | missense_variant | 1/7 | ENST00000377075.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNNM4 | ENST00000377075.3 | c.47G>A | p.Arg16His | missense_variant | 1/7 | 1 | NM_020184.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000732 AC: 11AN: 150240Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000406 AC: 44AN: 1082800Hom.: 0 Cov.: 31 AF XY: 0.0000450 AC XY: 23AN XY: 511664
GnomAD4 genome AF: 0.0000732 AC: 11AN: 150348Hom.: 0 Cov.: 32 AF XY: 0.0000818 AC XY: 6AN XY: 73372
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 16 of the CNNM4 protein (p.Arg16His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CNNM4-related conditions. ClinVar contains an entry for this variant (Variation ID: 957264). 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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