NM_024069.4:c.41G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024069.4(KXD1):c.41G>A(p.Arg14His) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KXD1
NM_024069.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

Publications

1 publications found

Variant links:

Genes affected

KXD1 (HGNC:28420): (KxDL motif containing 1) Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

KXD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KXD1	NM_024069.4 link	c.41G>A	p.Arg14His	missense_variant	Exon 2 of 5	ENST00000222307.9	NP_076974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KXD1	ENST00000222307.9 link	c.41G>A	p.Arg14His	missense_variant	Exon 2 of 5	1	NM_024069.4	ENSP00000222307.3		Q9BQD3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249262

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111504

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000616

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.41G>A (p.R14H) alteration is located in exon 3 (coding exon 1) of the KXD1 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.0092

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.016

T;T;T;.;.;T;T;.;T;.;T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

.;D;.;D;D;.;.;D;.;D;.;D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.60

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.9

L;L;L;.;.;.;L;.;L;.;L;.;.

PhyloP100

4.6

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;N;N;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.14

Sift

Benign

0.072

T;T;T;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.18

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.90

P;P;P;.;.;.;P;.;P;.;P;.;.

Vest4

0.40

MutPred

0.64

Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);Gain of catalytic residue at L16 (P = 0.0487);

MVP

0.63

MPC

1.3

ClinPred

0.79

GERP RS

5.4

PromoterAI

0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.87

Mutation Taster

=38/62

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_024069.4:c.41G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over