Variant 13-30210436-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032116.5(KATNAL1):c.1154G>C(p.Gly385Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,596,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

KATNAL1
NM_032116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.85

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNAL1	NM_032116.5 linkuse as main transcript	c.1154G>C	p.Gly385Ala	missense_variant	10/11	ENST00000380615.8	NP_115492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KATNAL1	ENST00000380615.8 linkuse as main transcript	c.1154G>C	p.Gly385Ala	missense_variant	10/11	1	NM_032116.5	ENSP00000369989	P1
KATNAL1	ENST00000380617.7 linkuse as main transcript	c.1154G>C	p.Gly385Ala	missense_variant	10/11	2		ENSP00000369991	P1
KATNAL1	ENST00000480854.1 linkuse as main transcript	n.229G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000172

AC:

AN:

232516

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

125914

show subpopulations

Gnomad AFR exome

AF:

0.0000654

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:

0.0000277

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1444212

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

718228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

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:

0.0000244

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000165

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

May 30, 2023

The c.1154G>C (p.G385A) alteration is located in exon 10 (coding exon 9) of the KATNAL1 gene. This alteration results from a G to C substitution at nucleotide position 1154, causing the glycine (G) at amino acid position 385 to be replaced by an alanine (A). 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

Pathogenic

0.69

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.74

D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

0.14

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Pathogenic

0.74

Sift

Benign

0.16

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.86

P;P

Vest4

0.73

MutPred

0.58

Loss of methylation at R386 (P = 0.0918);Loss of methylation at R386 (P = 0.0918);

MVP

0.89

MPC

0.61

ClinPred

0.76

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.85

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.

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