6-18197201-G-T

Variant names:

• chr6-18197201-G-T
• rs147829792
• NM_001364614.2:c.1114G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001364614.2(KDM1B):​c.1114G>T​(p.Asp372Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D372N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM1B NM_001364614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29247946).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364614.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	NM_001364614.2	MANE Select	c.1114G>T	p.Asp372Tyr	missense	Exon 11 of 22	NP_001351543.1	Q8NB78-1
	KDM1B	NM_001439117.1		c.1141G>T	p.Asp381Tyr	missense	Exon 12 of 23	NP_001426046.1
	KDM1B	NM_001439118.1		c.1141G>T	p.Asp381Tyr	missense	Exon 12 of 23	NP_001426047.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1B	ENST00000650836.2	MANE Select	c.1114G>T	p.Asp372Tyr	missense	Exon 11 of 22	ENSP00000499208.1	Q8NB78-1
	KDM1B	ENST00000546309.6	TSL:1	c.-18-17806G>T		intron	N/A	ENSP00000442670.1	Q08EI0
	KDM1B	ENST00000449850.2	TSL:5	c.1114G>T	p.Asp372Tyr	missense	Exon 11 of 22	ENSP00000405669.2	H0Y6H0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
PhyloP100		5.6
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.14
Sift	Benign	0.039	D
Sift4G	Uncertain	0.047	D
Vest4		0.75
MutPred		0.49		Loss of solvent accessibility (P = 0.0169)
MVP		0.15
MPC		0.42
ClinPred		0.81	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.69
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs147829792; hg19: chr6-18197432;