6-18162869-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001364614.2(KDM1B):​c.250C>T​(p.His84Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,638 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

KDM1B
NM_001364614.2 missense

Scores

8
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40
Variant links:
Genes affected
KDM1B (HGNC:21577): (lysine demethylase 1B) Flavin-dependent histone demethylases, such as KDM1B, regulate histone lysine methylation, an epigenetic mark that regulates gene expression and chromatin function (Karytinos et al., 2009 [PubMed 19407342]).[supplied by OMIM, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
KDM1BNM_001364614.2 linkc.250C>T p.His84Tyr missense_variant Exon 5 of 22 ENST00000650836.2 NP_001351543.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM1BENST00000650836.2 linkc.250C>T p.His84Tyr missense_variant Exon 5 of 22 NM_001364614.2 ENSP00000499208.1 Q8NB78-1
KDM1BENST00000546309.6 linkc.-19+7456C>T intron_variant Intron 1 of 3 1 ENSP00000442670.1 Q08EI0
KDM1BENST00000449850.2 linkc.250C>T p.His84Tyr missense_variant Exon 5 of 22 5 ENSP00000405669.2 H0Y6H0
KDM1BENST00000297792.9 linkc.250C>T p.His84Tyr missense_variant Exon 5 of 18 2 ENSP00000297792.5 Q8NB78-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251412
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1459638
Hom.:
0
Cov.:
28
AF XY:
0.00000964
AC XY:
7
AN XY:
726318
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.250C>T (p.H84Y) alteration is located in exon 5 (coding exon 3) of the KDM1B gene. This alteration results from a C to T substitution at nucleotide position 250, causing the histidine (H) at amino acid position 84 to be replaced by a tyrosine (Y). 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
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
28
DANN
Uncertain
1.0
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.090
D
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.0
.;M
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.3
.;N
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
.;D
Vest4
0.68
MutPred
0.56
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP
0.47
MPC
1.2
ClinPred
0.92
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.98

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.

Other links and lift over

dbSNP: rs749869144; hg19: chr6-18163100; API