2-96761090-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020184.4(CNNM4):āc.91T>Cā(p.Trp31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,515,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_020184.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNNM4 | NM_020184.4 | c.91T>C | p.Trp31Arg | missense_variant | 1/7 | ENST00000377075.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNNM4 | ENST00000377075.3 | c.91T>C | p.Trp31Arg | missense_variant | 1/7 | 1 | NM_020184.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000159 AC: 24AN: 150760Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000147 AC: 26AN: 177062Hom.: 0 AF XY: 0.000125 AC XY: 12AN XY: 95794
GnomAD4 exome AF: 0.000231 AC: 315AN: 1364790Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 153AN XY: 668562
GnomAD4 genome AF: 0.000159 AC: 24AN: 150760Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 9AN XY: 73608
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 31 of the CNNM4 protein (p.Trp31Arg). This variant is present in population databases (rs760633483, gnomAD 0.03%). 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: 288785). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 12, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.91T>C (p.W31R) alteration is located in exon 1 (coding exon 1) of the CNNM4 gene. This alteration results from a T to C substitution at nucleotide position 91, causing the tryptophan (W) at amino acid position 31 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Jalili syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at