Variant 13-30255603-C-G 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.336G>C(p.Gln112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,453,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

KATNAL1
NM_032116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.126

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=0.15619832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNAL1	NM_032116.5 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	4/11	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.336G>C	p.Gln112His	missense_variant	4/11	1	NM_032116.5	ENSP00000369989	P1
KATNAL1	ENST00000380617.7 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	4/11	2		ENSP00000369991	P1
KATNAL1	ENST00000414289.5 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	4/4	4		ENSP00000397776
KATNAL1	ENST00000441394.1 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	4/4	3		ENSP00000407792

Frequencies

GnomAD3 genomes

AF:

0.0000665

AC:

AN:

135290

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:

0.000137

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

180180

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

99696

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000560

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000105

AC:

139

AN:

1318476

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

654092

show subpopulations

Gnomad4 AFR exome

AF:

0.0000360

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:

0.000132

Gnomad4 OTH exome

AF:

0.0000187

GnomAD4 genome

AF:

0.0000665

AC:

AN:

135290

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

63940

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:

0.000137

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000274

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

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

Dec 16, 2022

The c.336G>C (p.Q112H) alteration is located in exon 4 (coding exon 3) of the KATNAL1 gene. This alteration results from a G to C substitution at nucleotide position 336, causing the glutamine (Q) at amino acid position 112 to be replaced by a histidine (H). 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

0.10

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;T;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.63

.;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.55

N;N;.;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.54

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.20

T;T;D;T

Sift4G

Benign

0.15

T;T;T;.

Polyphen

0.041

B;B;.;.

Vest4

0.31

MutPred

0.26

Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);

MVP

0.62

MPC

0.41

ClinPred

0.073

GERP RS

3.6

Varity_R

0.030

gMVP

0.25

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