2-86456416-ATTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTT

Variant names:

• chr2-86456416-A-ATTTTTT
• rs11431031
• NM_018433.6:c.557-9_557-4dupTTTTTT

Variant summary

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

The NM_018433.6(KDM3A):​c.557-9_557-4dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000081 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: KDM3A NM_018433.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593
• Publications: 1 publications found

Genes affected

KDM3A (HGNC:20815): (lysine demethylase 3A) Enables androgen receptor binding activity; histone H3-methyl-lysine-9 demethylase activity; and iron ion binding activity. Involved in several processes, including androgen receptor signaling pathway; formaldehyde biosynthetic process; and histone H3-K9 demethylation. Located in nucleoplasm. Implicated in cervical cancer and colon cancer. Biomarker of Ewing sarcoma; hepatocellular carcinoma; nasopharynx carcinoma; and prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018433.6. 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
	KDM3A	NM_018433.6	MANE Select	c.557-9_557-4dupTTTTTT		splice_region intron	N/A	NP_060903.2
	KDM3A	NM_001146688.2		c.557-9_557-4dupTTTTTT		splice_region intron	N/A	NP_001140160.1	Q9Y4C1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM3A	ENST00000312912.10	TSL:1 MANE Select	c.557-26_557-25insTTTTTT		intron	N/A	ENSP00000323659.5	Q9Y4C1
	KDM3A	ENST00000409064.5	TSL:1	c.557-26_557-25insTTTTTT		intron	N/A	ENSP00000386516.1	Q9Y4C1
	KDM3A	ENST00000900202.1		c.557-26_557-25insTTTTTT		intron	N/A	ENSP00000570261.1

Frequencies

GnomAD3 genomes AF: 0.00000805 AC: 1 AN: 124200 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000164

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 23 AN: 933634 Hom.: 0 Cov.: 0 AF XY: 0.0000325 AC XY: 15 AN XY: 462156

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18308

American (AMR) AF: 0.0000886 AC: 1 AN: 11292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15228

East Asian (EAS) AF: 0.0000416 AC: 1 AN: 24038

South Asian (SAS) AF: 0.0000691 AC: 3 AN: 43444

European-Finnish (FIN) AF: 0.0000836 AC: 3 AN: 35878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2664

European-Non Finnish (NFE) AF: 0.0000202 AC: 15 AN: 744308

Other (OTH) AF: 0.00 AC: 0 AN: 38474

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000012656), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000805 AC: 1 AN: 124200 Hom.: 0 Cov.: 0 AF XY: 0.0000172 AC XY: 1 AN XY: 58216

African (AFR) AF: 0.00 AC: 0 AN: 32426

American (AMR) AF: 0.00 AC: 0 AN: 11936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3206

East Asian (EAS) AF: 0.00 AC: 0 AN: 4330

South Asian (SAS) AF: 0.00 AC: 0 AN: 3914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.0000164 AC: 1 AN: 61128

Other (OTH) AF: 0.00 AC: 0 AN: 1650

Alfa AF: 0.00 Hom.: 1296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59

Splicing

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

Other links and lift over

dbSNP: rs11431031; hg19: chr2-86683539;