13-30283702-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032116.5(KATNAL1):āc.76A>Gā(p.Met26Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00027 ( 1 hom., cov: 32)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
KATNAL1
NM_032116.5 missense
NM_032116.5 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.48
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10242918).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KATNAL1 | NM_032116.5 | c.76A>G | p.Met26Val | missense_variant | 2/11 | ENST00000380615.8 | NP_115492.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KATNAL1 | ENST00000380615.8 | c.76A>G | p.Met26Val | missense_variant | 2/11 | 1 | NM_032116.5 | ENSP00000369989 | P1 | |
KATNAL1 | ENST00000380617.7 | c.76A>G | p.Met26Val | missense_variant | 2/11 | 2 | ENSP00000369991 | P1 | ||
KATNAL1 | ENST00000414289.5 | c.76A>G | p.Met26Val | missense_variant | 2/4 | 4 | ENSP00000397776 | |||
KATNAL1 | ENST00000441394.1 | c.76A>G | p.Met26Val | missense_variant | 2/4 | 3 | ENSP00000407792 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152192Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251442Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135896
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461756Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727190
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GnomAD4 genome AF: 0.000269 AC: 41AN: 152192Hom.: 1 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74338
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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 04, 2024 | The c.76A>G (p.M26V) alteration is located in exon 2 (coding exon 1) of the KATNAL1 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the methionine (M) at amino acid position 26 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;.
Polyphen
B;B;.;.
Vest4
MutPred
Gain of phosphorylation at Y28 (P = 0.1055);Gain of phosphorylation at Y28 (P = 0.1055);Gain of phosphorylation at Y28 (P = 0.1055);Gain of phosphorylation at Y28 (P = 0.1055);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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