13-30283646-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032116.5(KATNAL1):​c.132A>T​(p.Arg44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KATNAL1
NM_032116.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.489
Variant links:
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=0.19215506).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KATNAL1NM_032116.5 linkuse as main transcriptc.132A>T p.Arg44Ser missense_variant 2/11 ENST00000380615.8 NP_115492.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KATNAL1ENST00000380615.8 linkuse as main transcriptc.132A>T p.Arg44Ser missense_variant 2/111 NM_032116.5 ENSP00000369989 P1
KATNAL1ENST00000380617.7 linkuse as main transcriptc.132A>T p.Arg44Ser missense_variant 2/112 ENSP00000369991 P1
KATNAL1ENST00000414289.5 linkuse as main transcriptc.132A>T p.Arg44Ser missense_variant 2/44 ENSP00000397776
KATNAL1ENST00000441394.1 linkuse as main transcriptc.132A>T p.Arg44Ser missense_variant 2/43 ENSP00000407792

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 28, 2023The c.132A>T (p.R44S) alteration is located in exon 2 (coding exon 1) of the KATNAL1 gene. This alteration results from a A to T substitution at nucleotide position 132, causing the arginine (R) at amino acid position 44 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.021
T;T;.;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.59
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.87
.;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.19
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;L;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.39
N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.72
T;T;T;T
Sift4G
Benign
0.75
T;T;T;.
Polyphen
0.049
B;B;.;.
Vest4
0.73
MutPred
0.47
Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);
MVP
0.85
MPC
0.35
ClinPred
0.21
T
GERP RS
0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-30857783; API