6-18171384-T-A

Position:

• chr6-18171384-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001364614.2(KDM1B):​c.439T>A​(p.Cys147Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM1B NM_001364614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM1B	NM_001364614.2	c.439T>A	p.Cys147Ser	missense_variant	7/22	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM1B	ENST00000650836.2	c.439T>A	p.Cys147Ser	missense_variant	7/22		NM_001364614.2	ENSP00000499208.1
KDM1B	ENST00000546309.6	c.-19+15971T>A		intron_variant		1		ENSP00000442670.1
KDM1B	ENST00000449850.2	c.439T>A	p.Cys147Ser	missense_variant	7/22	5		ENSP00000405669.2
KDM1B	ENST00000297792.9	c.439T>A	p.Cys147Ser	missense_variant	7/18	2		ENSP00000297792.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Mar 02, 2023

The c.439T>A (p.C147S) alteration is located in exon 7 (coding exon 5) of the KDM1B gene. This alteration results from a T to A substitution at nucleotide position 439, causing the cysteine (C) at amino acid position 147 to be replaced by a serine (S). 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	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	.;N
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Vest4		0.89
MutPred		0.83		Gain of disorder (P = 0.0217);Gain of disorder (P = 0.0217);
MVP		0.95
MPC		1.2
ClinPred		0.99	D
GERP RS		5.4
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-18171615;