5-138381576-GCG-CCC

Variant names:

• chr5-138381576-GCG-CCC
• NM_016604.4:c.766_768delGCGinsCCC
• KDM3B p.Ala256Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016604.4(KDM3B):​c.766_768delGCGinsCCC​(p.Ala256Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A256V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KDM3B NM_016604.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Diets-Jongmans syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016604.4. 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
	KDM3B	NM_016604.4	MANE Select	c.766_768delGCGinsCCC	p.Ala256Pro	missense	N/A	NP_057688.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM3B	ENST00000314358.10	TSL:1 MANE Select	c.766_768delGCGinsCCC	p.Ala256Pro	missense	N/A	ENSP00000326563.5	Q7LBC6-1
	KDM3B	ENST00000510866.5	TSL:1	n.574_576delGCGinsCCC		non_coding_transcript_exon	Exon 5 of 24	ENSP00000425186.1	H0Y9V5
	KDM3B	ENST00000938919.1		c.766_768delGCGinsCCC	p.Ala256Pro	missense	N/A	ENSP00000608978.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-137717265;