chr20-3471115-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_139321.3(ATRN):c.8C>T(p.Ala3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,338 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_139321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATRN | NM_139321.3 | c.8C>T | p.Ala3Val | missense_variant | Exon 1 of 29 | ENST00000262919.10 | NP_647537.1 | |
ATRN | NM_001323332.2 | c.8C>T | p.Ala3Val | missense_variant | Exon 1 of 26 | NP_001310261.1 | ||
ATRN | NM_139322.4 | c.8C>T | p.Ala3Val | missense_variant | Exon 1 of 25 | NP_647538.1 | ||
ATRN | NM_001207047.3 | c.43C>T | p.Leu15Leu | synonymous_variant | Exon 1 of 25 | NP_001193976.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000930 AC: 1AN: 107488Hom.: 0 AF XY: 0.0000167 AC XY: 1AN XY: 59754
GnomAD4 exome AF: 7.36e-7 AC: 1AN: 1358338Hom.: 0 Cov.: 33 AF XY: 0.00000149 AC XY: 1AN XY: 670288
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3 of the ATRN protein (p.Ala3Val). 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 ATRN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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