chr13-30231382-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032116.5(KATNAL1):āc.817T>Cā(p.Ser273Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,610,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000023 ( 0 hom. )
Consequence
KATNAL1
NM_032116.5 missense
NM_032116.5 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
KATNAL1 (HGNC:28361): (katanin catalytic subunit A1 like 1) Enables identical protein binding activity and microtubule-severing ATPase activity. Involved in microtubule severing. Located in cytoplasm; microtubule; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.93
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KATNAL1 | NM_032116.5 | c.817T>C | p.Ser273Pro | 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.817T>C | p.Ser273Pro | missense_variant | 7/11 | 1 | NM_032116.5 | ENSP00000369989 | P1 | |
KATNAL1 | ENST00000380617.7 | c.817T>C | p.Ser273Pro | missense_variant | 7/11 | 2 | ENSP00000369991 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248604Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134292
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1457804Hom.: 0 Cov.: 30 AF XY: 0.0000262 AC XY: 19AN XY: 724898
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 24, 2024 | The c.817T>C (p.S273P) alteration is located in exon 7 (coding exon 6) of the KATNAL1 gene. This alteration results from a T to C substitution at nucleotide position 817, causing the serine (S) at amino acid position 273 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at