chr20-35669638-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021100.5(NFS1):c.1358A>G(p.Lys453Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K453T) has been classified as Uncertain significance.
Frequency
Consequence
NM_021100.5 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 |
---|---|---|---|---|---|---|---|
NFS1 | NM_021100.5 | c.1358A>G | p.Lys453Arg | missense_variant | 13/13 | ENST00000374092.9 | |
NFS1 | NM_001198989.2 | c.1205A>G | p.Lys402Arg | missense_variant | 12/12 | ||
NFS1 | NR_037570.3 | n.1544A>G | non_coding_transcript_exon_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFS1 | ENST00000374092.9 | c.1358A>G | p.Lys453Arg | missense_variant | 13/13 | 1 | NM_021100.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251446Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135910
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461782Hom.: 0 Cov.: 30 AF XY: 0.0000894 AC XY: 65AN XY: 727194
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 11, 2022 | The c.1358A>G (p.K453R) alteration is located in exon 13 (coding exon 13) of the NFS1 gene. This alteration results from a A to G substitution at nucleotide position 1358, causing the lysine (K) at amino acid position 453 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 453 of the NFS1 protein (p.Lys453Arg). This variant is present in population databases (rs145410950, gnomAD 0.02%). 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: 1395310). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at