Genetic Variant KLHL21:c.*1697G>A (chr1-6591668-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014851.4(KLHL21):c.*1697G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,194 control chromosomes in the GnomAD database, including 6,088 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 0.28 ( 6079 hom., cov: 33)

Exomes 𝑓: 0.36 ( 9 hom. )

Consequence

KLHL21
NM_014851.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL21	NM_014851.4 link	c.*1697G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000377658.8	NP_055666.2	Q9UJP4-1
KLHL21	NM_001324309.2 link	c.*2440G>A		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 link	c.*1697G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_014851.4	ENSP00000366886.4		Q9UJP4-1
KLHL21	ENST00000377663 link	c.*3697G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000366891.3		Q9UJP4-2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42247

AN:

151948

Hom.:

6076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.298

GnomAD4 exome

AF:

0.359

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.391

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.278

AC:

42255

AN:

152066

Hom.:

6079

Cov.:

AF XY:

0.276

AC XY:

20518

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.321

Hom.:

10087

Bravo

AF:

0.271

Asia WGS

AF:

0.202

AC:

706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.64

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over