dbSNP rs759110549: KLHL23:p.Arg105Lys (chr2-169735328-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144711.6(KLHL23):c.314G>A(p.Arg105Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KLHL23
NM_144711.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

KLHL23 (HGNC:27506): (kelch like family member 23)

KLHL23 links:

PHOSPHO2-KLHL23 (HGNC:):

PHOSPHO2-KLHL23 links:

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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=0.23594227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL23	NM_144711.6 link	c.314G>A	p.Arg105Lys	missense_variant	Exon 2 of 4	ENST00000392647.7	NP_653312.2	Q8NBE8
PHOSPHO2-KLHL23	NM_001199290.3 link	c.314G>A	p.Arg105Lys	missense_variant	Exon 4 of 6		NP_001186219.1	Q8NBE8
PHOSPHO2-KLHL23	NR_144936.2 link	n.359-6057G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL23	ENST00000392647.7 link	c.314G>A	p.Arg105Lys	missense_variant	Exon 2 of 4	1	NM_144711.6	ENSP00000376419.2		Q8NBE8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.50

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.28

N;N

REVEL

Benign

0.098

Sift

Benign

0.44

T;T

Sift4G

Benign

0.92

T;T

Polyphen

0.035

B;B

Vest4

0.16

MutPred

0.37

Gain of methylation at R105 (P = 0.0168);Gain of methylation at R105 (P = 0.0168);

MVP

0.72

MPC

0.10

ClinPred

0.40

GERP RS

5.8

Varity_R

0.19

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over