Genetic Variant KATNBL1:p.Glu277Lys (chr15-34145451-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_024713.3(KATNBL1):c.829G>A(p.Glu277Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,463,362 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 7 hom. )

Consequence

KATNBL1
NM_024713.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

1 publications found

Variant links:

Genes affected

KATNBL1 (HGNC:26199): (katanin regulatory subunit B1 like 1) Predicted to enable microtubule binding activity. Involved in positive regulation of cytoskeleton organization. Located in several cellular components, including cleavage furrow; mitotic spindle pole; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

KATNBL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056507587).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00645 (980/151932) while in subpopulation AFR AF = 0.0228 (943/41432). AF 95% confidence interval is 0.0216. There are 11 homozygotes in GnomAd4. There are 460 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNBL1	NM_024713.3 link	c.829G>A	p.Glu277Lys	missense_variant	Exon 9 of 10	ENST00000256544.8	NP_078989.1	Q9H079A0A024R9P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNBL1	ENST00000256544.8 link	c.829G>A	p.Glu277Lys	missense_variant	Exon 9 of 10	1	NM_024713.3	ENSP00000256544.3		Q9H079

Frequencies

GnomAD3 genomes

AF:

0.00644

AC:

978

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00432

GnomAD2 exomes

AF:

0.00135

AC:

199

AN:

147208

AF XY:

0.000861

show subpopulations

Gnomad AFR exome

AF:

0.0212

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000547

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000528

AC:

693

AN:

1311430

Hom.:

Cov.:

AF XY:

0.000420

AC XY:

272

AN XY:

647538

show subpopulations

African (AFR)

AF:

0.0214

AC:

558

AN:

26106

American (AMR)

AF:

0.00148

AC:

AN:

20988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21326

East Asian (EAS)

AF:

0.0000307

AC:

AN:

32624

South Asian (SAS)

AF:

0.0000173

AC:

AN:

57942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48862

Middle Eastern (MID)

AF:

0.00141

AC:

AN:

4976

European-Non Finnish (NFE)

AF:

0.0000201

AC:

AN:

1045182

Other (OTH)

AF:

0.00139

AC:

AN:

53424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00645

AC:

980

AN:

151932

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

460

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0228

AC:

943

AN:

41432

American (AMR)

AF:

0.00171

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.00427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

137

183

229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.00742

ESP6500AA

AF:

0.0167

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00174

AC:

210

Asia WGS

AF:

0.00116

AC:

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.075

N;.;.

PhyloP100

1.5

PrimateAI

Benign

0.41

PROVEAN

Benign

0.54

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.85

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.27

MVP

0.18

MPC

0.13

ClinPred

0.014

GERP RS

4.3

Varity_R

0.071

gMVP

0.30

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over