NM_018433.6:c.557-9_557-4delTTTTTT

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018433.6(KDM3A):​c.557-9_557-4delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 933,624 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: KDM3A NM_018433.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6	c.557-9_557-4delTTTTTT		splice_region_variant, intron_variant	Intron 5 of 25	ENST00000312912.10	NP_060903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3A	ENST00000312912.10	c.557-25_557-20delTTTTTT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000139 AC: 13 AN: 933624 Hom.: 0 AF XY: 0.00000866 AC XY: 4 AN XY: 462142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000886

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000460

Gnomad4 FIN exome AF: 0.0000279

Gnomad4 NFE exome AF: 0.0000107

Gnomad4 OTH exome AF: 0.0000260

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11431031; hg19: chr2-86683539;