6-18200574-C-G

Position:

• chr6-18200574-C-G

Variant summary

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

The NM_001364614.2(KDM1B):​c.1357C>G​(p.Gln453Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM1B NM_001364614.2 missense, splice_region
• Scores: Splicing: ADA: 0.9253
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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]

ACMG classification

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	c.1357C>G	p.Gln453Glu	missense_variant, splice_region_variant	13/22	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM1B	ENST00000650836.2	c.1357C>G	p.Gln453Glu	missense_variant, splice_region_variant	13/22		NM_001364614.2	ENSP00000499208.1
KDM1B	ENST00000546309.6	c.-18-14433C>G		intron_variant		1		ENSP00000442670.1
KDM1B	ENST00000449850.2	c.1357C>G	p.Gln453Glu	missense_variant, splice_region_variant	13/22	5		ENSP00000405669.2
KDM1B	ENST00000297792.9	c.961C>G	p.Gln321Glu	missense_variant, splice_region_variant	11/18	2		ENSP00000297792.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.961C>G (p.Q321E) alteration is located in exon 11 (coding exon 9) of the KDM1B gene. This alteration results from a C to G substitution at nucleotide position 961, causing the glutamine (Q) at amino acid position 321 to be replaced by a glutamic acid (E). 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	0.56
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	0.44	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.87	.;N
REVEL	Benign	0.19
Sift	Benign	0.56	.;T
Sift4G	Benign	0.15	.;T
Vest4		0.75
MutPred		0.39		Loss of helix (P = 0.1706);.;
MVP		0.55
MPC		0.37
ClinPred		0.88	D
GERP RS		5.4
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Benign	0.63
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.

Other links and lift over

hg19: chr6-18200805;