Variant 6-18171364-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001364614.2(KDM1B):c.419T>C(p.Val140Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000317 in 1,512,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

KDM1B
NM_001364614.2 missense, splice_region

Scores

Splicing: ADA: 0.02717

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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]

KDM1B links:

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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/exons	MANE	Protein	UniProt
KDM1B	NM_001364614.2 linkuse as main transcript	c.419T>C	p.Val140Ala	missense_variant, splice_region_variant	7/22	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDM1B	ENST00000650836.2 linkuse as main transcript	c.419T>C	p.Val140Ala	missense_variant, splice_region_variant	7/22		NM_001364614.2	ENSP00000499208.1	Q8NB78-1
KDM1B	ENST00000546309.6 linkuse as main transcript	c.-19+15951T>C		intron_variant		1		ENSP00000442670.1	Q08EI0
KDM1B	ENST00000449850.2 linkuse as main transcript	c.419T>C	p.Val140Ala	missense_variant, splice_region_variant	7/22	5		ENSP00000405669.2	H0Y6H0
KDM1B	ENST00000297792.9 linkuse as main transcript	c.419T>C	p.Val140Ala	missense_variant, splice_region_variant	7/18	2		ENSP00000297792.5	Q8NB78-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152200

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251366

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135854

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000331

AC:

AN:

1360140

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

682602

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000412

Gnomad4 OTH exome

AF:

0.0000351

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.419T>C (p.V140A) alteration is located in exon 7 (coding exon 5) of the KDM1B gene. This alteration results from a T to C substitution at nucleotide position 419, causing the valine (V) at amino acid position 140 to be replaced by an alanine (A). 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

Uncertain

0.50

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.98

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.23

Sift

Benign

0.13

.;T

Sift4G

Benign

0.15

.;T

Vest4

0.35

MutPred

0.73

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.70

MPC

1.2

ClinPred

0.75

GERP RS

5.4

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.027

dbscSNV1_RF

Benign

0.28

SpliceAI score (max)

0.080

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over