2-86456416-ATTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr2-86456416-A-ATTTTTTTTTTT
• rs11431031
• NM_018433.6:c.557-14_557-4dupTTTTTTTTTTT

Variant summary

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

The NM_018433.6(KDM3A):​c.557-14_557-4dupTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

• Frequency:
  • Genomes: 𝑓 0.0000081 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000021 (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.557-14_557-4dupTTTTTTTTTTT		splice_region intron	N/A	NP_060903.2
	KDM3A	NM_001146688.2		c.557-14_557-4dupTTTTTTTTTTT		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_557-25insTTTTTTTTTTT		intron	N/A	ENSP00000323659.5	Q9Y4C1
	KDM3A	ENST00000409064.5	TSL:1	c.557-26_557-25insTTTTTTTTTTT		intron	N/A	ENSP00000386516.1	Q9Y4C1
	KDM3A	ENST00000900202.1		c.557-26_557-25insTTTTTTTTTTT		intron	N/A	ENSP00000570261.1

Frequencies

GnomAD3 genomes AF: 0.00000805 AC: 1 AN: 124204 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000308

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 2 AN: 933664 Hom.: 0 Cov.: 0 AF XY: 0.00000216 AC XY: 1 AN XY: 462170

⚠️ 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: 0.00 AC: 0 AN: 11292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 24038

South Asian (SAS) AF: 0.0000230 AC: 1 AN: 43448

European-Finnish (FIN) AF: 0.0000279 AC: 1 AN: 35878

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 744332

Other (OTH) AF: 0.00 AC: 0 AN: 38476

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000805 AC: 1 AN: 124204 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 58220

African (AFR) AF: 0.0000308 AC: 1 AN: 32430

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: 0.00 AC: 0 AN: 61128

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

Alfa AF: 0.00558 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;