chr13-30255472-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032116.5(KATNAL1):ā€‹c.467A>Gā€‹(p.Tyr156Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,586,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000091 ( 0 hom. )

Consequence

KATNAL1
NM_032116.5 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.664
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.025548935).
BP6
Variant 13-30255472-T-C is Benign according to our data. Variant chr13-30255472-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3112798.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KATNAL1NM_032116.5 linkuse as main transcriptc.467A>G p.Tyr156Cys missense_variant 4/11 ENST00000380615.8 NP_115492.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KATNAL1ENST00000380615.8 linkuse as main transcriptc.467A>G p.Tyr156Cys missense_variant 4/111 NM_032116.5 ENSP00000369989 P1
KATNAL1ENST00000380617.7 linkuse as main transcriptc.467A>G p.Tyr156Cys missense_variant 4/112 ENSP00000369991 P1
KATNAL1ENST00000414289.5 linkuse as main transcript downstream_gene_variant 4 ENSP00000397776
KATNAL1ENST00000441394.1 linkuse as main transcript downstream_gene_variant 3 ENSP00000407792

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152088
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000172
AC:
4
AN:
231894
Hom.:
0
AF XY:
0.00000791
AC XY:
1
AN XY:
126344
show subpopulations
Gnomad AFR exome
AF:
0.000141
Gnomad AMR exome
AF:
0.0000322
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000349
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000907
AC:
13
AN:
1433988
Hom.:
0
Cov.:
31
AF XY:
0.00000420
AC XY:
3
AN XY:
713608
show subpopulations
Gnomad4 AFR exome
AF:
0.000126
Gnomad4 AMR exome
AF:
0.0000238
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000241
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000455
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152088
Hom.:
0
Cov.:
31
AF XY:
0.0000673
AC XY:
5
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 10, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
6.9
DANN
Benign
0.38
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.16
.;T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.026
T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
1.1
L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.33
N;N
REVEL
Uncertain
0.29
Sift
Benign
0.12
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.0
B;B
Vest4
0.069
MVP
0.30
MPC
0.38
ClinPred
0.027
T
GERP RS
-11
Varity_R
0.050
gMVP
0.35

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

LitVar

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

Other links and lift over

dbSNP: rs377222240; hg19: chr13-30829609; API