Variant rs7233515 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001387690.1(KATNAL2):c.479G>A(p.Ser160Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,608,632 control chromosomes in the GnomAD database, including 134,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12195 hom., cov: 33)

Exomes 𝑓: 0.41 ( 122778 hom. )

Consequence

KATNAL2
NM_001387690.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.903

Variant links:

Genes affected

KATNAL2 (HGNC:25387): (katanin catalytic subunit A1 like 2) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Located in cytoplasm; microtubule; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

KATNAL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.368946E-5).

BP6

Variant 18-47059584-G-A is Benign according to our data. Variant chr18-47059584-G-A is described in ClinVar as [Benign]. Clinvar id is 587805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNAL2	NM_001387690.1 linkuse as main transcript	c.479G>A	p.Ser160Asn	missense_variant	8/18	ENST00000683218.1	NP_001374619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNAL2	ENST00000683218.1 linkuse as main transcript	c.479G>A	p.Ser160Asn	missense_variant	8/18		NM_001387690.1	ENSP00000508137	P1	Q8IYT4-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60759

AN:

151896

Hom.:

12190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.424

GnomAD3 exomes

AF:

0.430

AC:

108118

AN:

251168

Hom.:

23861

AF XY:

0.428

AC XY:

58094

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.354

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.490

Gnomad SAS exome

AF:

0.460

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.408

AC:

593871

AN:

1456620

Hom.:

122778

Cov.:

AF XY:

0.408

AC XY:

295938

AN XY:

724938

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.503

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.398

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.400

AC:

60790

AN:

152012

Hom.:

12195

Cov.:

AF XY:

0.402

AC XY:

29890

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.353

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.350

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.405

Hom.:

27332

Bravo

AF:

0.409

TwinsUK

AF:

0.405

AC:

1503

ALSPAC

AF:

0.407

AC:

1569

ESP6500AA

AF:

0.347

AC:

1529

ESP6500EA

AF:

0.400

AC:

3438

ExAC

AF:

0.423

AC:

51409

Asia WGS

AF:

0.489

AC:

1696

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2016

This alteration is classified as 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.31

DANN

Benign

0.84

DEOGEN2

Benign

0.027

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.000064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.51

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.22

.;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.093, 0.037

MPC

0.10

ClinPred

0.016

GERP RS

-4.8

Varity_R

0.041

gMVP

0.46

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