NM_018433.6:c.557-4delT

Variant names:

• chr2-86456416-AT-A
• rs11431031
• NM_018433.6:c.557-4delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018433.6(KDM3A):​c.557-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.0070 (3 hom., cov: 0)
  • Exomes 𝑓: 0.099 (2 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 869 AN: 124202 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00469

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.000624

Gnomad EAS AF: 0.000693

Gnomad SAS AF: 0.0115

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.00394

Gnomad NFE AF: 0.00777

Gnomad OTH AF: 0.00727

GnomAD3 exomes AF: 0.145 AC: 4509 AN: 31146 Hom.: 0 AF XY: 0.155 AC XY: 2685 AN XY: 17322

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.0900

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.0581

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.0987 AC: 89957 AN: 911854 Hom.: 2 Cov.: 0 AF XY: 0.101 AC XY: 45665 AN XY: 451178

Gnomad4 AFR exome AF: 0.0986

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.0717

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0843

Gnomad4 NFE exome AF: 0.0965

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.00701 AC: 870 AN: 124186 Hom.: 3 Cov.: 0 AF XY: 0.00764 AC XY: 445 AN XY: 58226

Gnomad4 AFR AF: 0.00471

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.000624

Gnomad4 EAS AF: 0.000695

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.00777

Gnomad4 OTH AF: 0.00726

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;