Variant chr13-30255481-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032116.5(KATNAL1):c.458A>T(p.Asp153Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000289 in 1,594,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

KATNAL1
NM_032116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

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]

KATNAL1 links:

Genome browser will be placed here

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=0.136076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNAL1	NM_032116.5 link	c.458A>T	p.Asp153Val	missense_variant	4/11	ENST00000380615.8	NP_115492.1	Q9BW62A0A024RDP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KATNAL1	ENST00000380615.8 link	c.458A>T	p.Asp153Val	missense_variant	4/11	1	NM_032116.5	ENSP00000369989.3	Q9BW62
KATNAL1	ENST00000380617.7 link	c.458A>T	p.Asp153Val	missense_variant	4/11	2		ENSP00000369991.3	Q9BW62
KATNAL1	ENST00000414289.5 link	c.458A>T	p.Asp153Val	missense_variant, splice_region_variant	4/4	4		ENSP00000397776.1	A2A3H2
KATNAL1	ENST00000441394.1 link	c.*7A>T		downstream_gene_variant		3		ENSP00000407792.1	Q5T558

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000422

AC:

AN:

236762

Hom.:

AF XY:

0.0000311

AC XY:

AN XY:

128734

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1442312

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

717742

show subpopulations

Gnomad4 AFR exome

AF:

0.000655

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.000151

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000556

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Aug 27, 2024

The c.458A>T (p.D153V) alteration is located in exon 4 (coding exon 3) of the KATNAL1 gene. This alteration results from a A to T substitution at nucleotide position 458, causing the aspartic acid (D) at amino acid position 153 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

0.18

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Uncertain

0.011

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.87

N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.28

T;T;D

Sift4G

Benign

0.31

T;T;D

Polyphen

0.0010

B;B;.

Vest4

0.42

MVP

0.87

MPC

0.43

ClinPred

0.085

GERP RS

5.3

Varity_R

0.16

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over