NM_018433.6:c.557-4dupT

Variant names:

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

Variant summary

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

The NM_018433.6(KDM3A):​c.557-4dupT 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 0.73 (33218 hom., cov: 0)
  • Exomes 𝑓: 0.37 (766 hom.)
  • Failed GnomAD Quality Control
• 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: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6	c.557-4dupT		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.557-26_557-25insT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5

Frequencies

GnomAD3 genomes AF: 0.728 AC: 90441 AN: 124176 Hom.: 33215 Cov.: 0

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.696

GnomAD3 exomes AF: 0.324 AC: 10092 AN: 31146 Hom.: 166 AF XY: 0.319 AC XY: 5525 AN XY: 17322

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.376

Gnomad SAS exome AF: 0.253

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.326

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.371 AC: 341222 AN: 920536 Hom.: 766 Cov.: 0 AF XY: 0.367 AC XY: 167268 AN XY: 455620

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.728 AC: 90433 AN: 124160 Hom.: 33218 Cov.: 0 AF XY: 0.722 AC XY: 42023 AN XY: 58208

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.697

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;