13-30240504-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032116.5(KATNAL1):ā€‹c.682A>Gā€‹(p.Met228Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 33)
Exomes š‘“: 0.000056 ( 0 hom. )

Consequence

KATNAL1
NM_032116.5 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KATNAL1NM_032116.5 linkuse as main transcriptc.682A>G p.Met228Val missense_variant 6/11 ENST00000380615.8 NP_115492.1
LOC102723381XR_007063741.1 linkuse as main transcriptn.280-750T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KATNAL1ENST00000380615.8 linkuse as main transcriptc.682A>G p.Met228Val missense_variant 6/111 NM_032116.5 ENSP00000369989 P1
KATNAL1ENST00000380617.7 linkuse as main transcriptc.682A>G p.Met228Val missense_variant 6/112 ENSP00000369991 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251302
Hom.:
0
AF XY:
0.0000884
AC XY:
12
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000561
AC:
82
AN:
1461548
Hom.:
0
Cov.:
30
AF XY:
0.0000591
AC XY:
43
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000403
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152354
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000384
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 GeneticsJul 05, 2023The c.682A>G (p.M228V) alteration is located in exon 6 (coding exon 5) of the KATNAL1 gene. This alteration results from a A to G substitution at nucleotide position 682, causing the methionine (M) at amino acid position 228 to be replaced by a valine (V). 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
Benign
0.14
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.23
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.23
T;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.078
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Uncertain
0.34
D
MutationAssessor
Pathogenic
3.2
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Uncertain
0.57
Sift
Benign
0.23
T;T
Sift4G
Benign
0.33
T;T
Polyphen
0.25
B;B
Vest4
0.75
MVP
0.87
MPC
0.38
ClinPred
0.27
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.67
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs182471772; hg19: chr13-30814641; API