chr2-86456416-ATTT-A

Variant names:

• chr2-86456416-ATTT-A
• rs11431031
• NM_018433.6:c.557-6_557-4delTTT

Variant summary

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

The NM_018433.6(KDM3A):​c.557-6_557-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,054,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. 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: 0.0019 (0 hom.)
• Consequence: KDM3A NM_018433.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593

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 1727 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6	c.557-6_557-4delTTT		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_557-23delTTT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5

Frequencies

GnomAD3 genomes AF: 0.00000805 AC: 1 AN: 124202 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

GnomAD3 exomes AF: 0.00517 AC: 161 AN: 31146 Hom.: 0 AF XY: 0.00554 AC XY: 96 AN XY: 17322

Gnomad AFR exome AF: 0.00705

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00600

Gnomad EAS exome AF: 0.00558

Gnomad SAS exome AF: 0.00778

Gnomad FIN exome AF: 0.00113

Gnomad NFE exome AF: 0.00470

Gnomad OTH exome AF: 0.0123

GnomAD4 exome AF: 0.00186 AC: 1727 AN: 929884 Hom.: 0 AF XY: 0.00195 AC XY: 899 AN XY: 460210

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00393

Gnomad4 ASJ exome AF: 0.00284

Gnomad4 EAS exome AF: 0.000960

Gnomad4 SAS exome AF: 0.00387

Gnomad4 FIN exome AF: 0.00129

Gnomad4 NFE exome AF: 0.00173

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00000805 AC: 1 AN: 124202 Hom.: 0 Cov.: 0 AF XY: 0.0000172 AC XY: 1 AN XY: 58218

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000164

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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;