rs548569136
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020921.4(NIN):c.3635C>T(p.Ala1212Val) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,614,078 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A1212A) has been classified as Likely benign.
Frequency
Consequence
NM_020921.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIN | NM_020921.4 | c.3635C>T | p.Ala1212Val | missense_variant | 18/31 | ENST00000530997.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIN | ENST00000530997.7 | c.3635C>T | p.Ala1212Val | missense_variant | 18/31 | 5 | NM_020921.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251362Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461868Hom.: 0 Cov.: 63 AF XY: 0.0000234 AC XY: 17AN XY: 727236
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74422
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 377176). This variant has not been reported in the literature in individuals affected with NIN-related conditions. This variant is present in population databases (rs548569136, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1212 of the NIN protein (p.Ala1212Val). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 31, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at