20-35669638-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021100.5(NFS1):c.1358A>C(p.Lys453Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 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. K453R) 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>C | p.Lys453Thr | missense_variant | 13/13 | ENST00000374092.9 | |
NFS1 | NM_001198989.2 | c.1205A>C | p.Lys402Thr | missense_variant | 12/12 | ||
NFS1 | NR_037570.3 | n.1544A>C | non_coding_transcript_exon_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFS1 | ENST00000374092.9 | c.1358A>C | p.Lys453Thr | missense_variant | 13/13 | 1 | NM_021100.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251446Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135910
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461782Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727194
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | The c.1358A>C (p.K453T) alteration is located in exon 13 (coding exon 13) of the NFS1 gene. This alteration results from a A to C substitution at nucleotide position 1358, causing the lysine (K) at amino acid position 453 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at