5-138381576-G-C

Position:

• chr5-138381576-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_016604.4(KDM3B):​c.766G>C​(p.Ala256Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. A256T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: KDM3B NM_016604.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

Genes affected

KDM3B (HGNC:1337): (lysine demethylase 3B) Predicted to enable chromatin DNA binding activity; histone H3-methyl-lysine-9 demethylase activity; and transcription coregulator activity. Predicted to be involved in histone H3-K9 demethylation and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of acute lymphoblastic leukemia; breast cancer; colorectal cancer; and lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

KDM3B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KDM3B. . Gene score misZ 4.9789 (greater than the threshold 3.09). Trascript score misZ 6.2129 (greater than threshold 3.09). GenCC has associacion of gene with Diets-Jongmans syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.058407664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3B	NM_016604.4	c.766G>C	p.Ala256Pro	missense_variant	6/24	ENST00000314358.10	NP_057688.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM3B	ENST00000314358.10	c.766G>C	p.Ala256Pro	missense_variant	6/24	1	NM_016604.4	ENSP00000326563.5
KDM3B	ENST00000510866.5	n.574G>C		non_coding_transcript_exon_variant	5/24	1		ENSP00000425186.1
KDM3B	ENST00000512928.1	n.455G>C		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.24
DANN	Benign	0.96
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.071
Sift	Benign	0.26	T
Sift4G	Benign	0.29	T
Polyphen		0.021	B
Vest4		0.27
MutPred		0.25		Gain of glycosylation at A256 (P = 0.0169);
MVP		0.61
MPC		0.74
ClinPred		0.044	T
GERP RS		-2.8
Varity_R		0.038
gMVP		0.19

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

Other links and lift over

dbSNP: rs6865472; hg19: chr5-137717265;