13-30231381-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_032116.5(KATNAL1):c.818C>T(p.Ser273Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,609,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032116.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KATNAL1 | NM_032116.5 | c.818C>T | p.Ser273Leu | missense_variant | 7/11 | ENST00000380615.8 | NP_115492.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KATNAL1 | ENST00000380615.8 | c.818C>T | p.Ser273Leu | missense_variant | 7/11 | 1 | NM_032116.5 | ENSP00000369989 | P1 | |
KATNAL1 | ENST00000380617.7 | c.818C>T | p.Ser273Leu | missense_variant | 7/11 | 2 | ENSP00000369991 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248412Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134198
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1457354Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 724684
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 25, 2023 | The c.818C>T (p.S273L) alteration is located in exon 7 (coding exon 6) of the KATNAL1 gene. This alteration results from a C to T substitution at nucleotide position 818, causing the serine (S) at amino acid position 273 to be replaced by a leucine (L). 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