20-35672770-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021100.5(NFS1):c.1295G>A(p.Arg432His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,274 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021100.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NFS1 | NM_021100.5 | c.1295G>A | p.Arg432His | missense_variant | Exon 12 of 13 | ENST00000374092.9 | NP_066923.3 | |
NFS1 | NM_001198989.2 | c.1142G>A | p.Arg381His | missense_variant | Exon 11 of 12 | NP_001185918.1 | ||
NFS1 | NR_037570.3 | n.1481G>A | non_coding_transcript_exon_variant | Exon 13 of 14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NFS1 | ENST00000374092.9 | c.1295G>A | p.Arg432His | missense_variant | Exon 12 of 13 | 1 | NM_021100.5 | ENSP00000363205.3 | ||
ENSG00000272897 | ENST00000541176.2 | n.272G>A | non_coding_transcript_exon_variant | Exon 4 of 9 | 2 | ENSP00000443983.2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251348Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135870
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1458976Hom.: 1 Cov.: 29 AF XY: 0.0000152 AC XY: 11AN XY: 726044
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 432 of the NFS1 protein (p.Arg432His). This variant is present in population databases (rs188144557, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with NFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2171344). 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 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at