Genetic Variant KLHL21:c.*2332C>T (chr1-6591033-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014851.4(KLHL21):c.*2332C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 398,592 control chromosomes in the GnomAD database, including 5,676 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1476 hom., cov: 33)

Exomes 𝑓: 0.16 ( 4200 hom. )

Consequence

KLHL21
NM_014851.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

18 publications found

Variant links:

Genes affected

KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

KLHL21 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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL21	NM_014851.4 link	c.*2332C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000377658.8	NP_055666.2	Q9UJP4-1
KLHL21	NM_001324309.2 link	c.*3075C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001311238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL21	ENST00000377658.8 link	c.*2332C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_014851.4	ENSP00000366886.4		Q9UJP4-1
KLHL21	ENST00000377663.3 link	c.*4332C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000366891.3		Q9UJP4-2

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17700

AN:

152164

Hom.:

1478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.0962

GnomAD4 exome

AF:

0.160

AC:

39453

AN:

246310

Hom.:

4200

Cov.:

AF XY:

0.159

AC XY:

19830

AN XY:

124814

show subpopulations

African (AFR)

AF:

0.0284

AC:

204

AN:

7180

American (AMR)

AF:

0.0645

AC:

479

AN:

7432

Ashkenazi Jewish (ASJ)

AF:

0.0491

AC:

454

AN:

9240

East Asian (EAS)

AF:

0.397

AC:

9094

AN:

22894

South Asian (SAS)

AF:

0.118

AC:

359

AN:

3032

European-Finnish (FIN)

AF:

0.168

AC:

3494

AN:

20832

Middle Eastern (MID)

AF:

0.0440

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.146

AC:

23073

AN:

158032

Other (OTH)

AF:

0.137

AC:

2239

AN:

16374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1696

3392

5087

6783

8479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.116

AC:

17695

AN:

152282

Hom.:

1476

Cov.:

AF XY:

0.117

AC XY:

8683

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0291

AC:

1209

AN:

41586

American (AMR)

AF:

0.0810

AC:

1239

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3472

East Asian (EAS)

AF:

0.400

AC:

2072

AN:

5174

South Asian (SAS)

AF:

0.107

AC:

518

AN:

4828

European-Finnish (FIN)

AF:

0.168

AC:

1776

AN:

10600

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.152

AC:

10323

AN:

68000

Other (OTH)

AF:

0.0980

AC:

207

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

794

1589

2383

3178

3972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.131

Hom.:

2816

Bravo

AF:

0.107

Asia WGS

AF:

0.231

AC:

803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.2

(source)

DANN

Benign

0.66

PhyloP100

0.055

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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