5-138352882-C-CGCGGCGGCA

Position:

• chr5-138352882-C-CGCGGCGGCA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_016604.4(KDM3B):​c.94_102dupGCAGCGGCG​(p.Ala32_Ala34dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000816 in 1,225,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: KDM3B NM_016604.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016604.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3B	NM_016604.4	c.94_102dupGCAGCGGCG	p.Ala32_Ala34dup	conservative_inframe_insertion	1/24	ENST00000314358.10	NP_057688.3
KDM3B	XM_005272018.5	c.94_102dupGCAGCGGCG	p.Ala32_Ala34dup	conservative_inframe_insertion	1/23		XP_005272075.1
KDM3B	XM_047417313.1	c.-955_-947dupGCAGCGGCG		5_prime_UTR_variant	1/25		XP_047273269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM3B	ENST00000314358.10	c.94_102dupGCAGCGGCG	p.Ala32_Ala34dup	conservative_inframe_insertion	1/24	1	NM_016604.4	ENSP00000326563.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.16e-7 AC: 1 AN: 1225622 Hom.: 0 Cov.: 35 AF XY: 0.00000166 AC XY: 1 AN XY: 602404

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000518

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

May 06, 2024

Variant summary: KDM3B c.94_102dupGCAGCGGCG (p.Ala32_Ala34dup) results in an in-frame duplication that is predicted to duplicate three amino acids into the encoded protein. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.94_102dupGCAGCGGCG in individuals affected with KDM3B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr5-137688571;