Genetic Variant KDM3A:c.557-5_557-4dupTT (chr2-86456416-A-ATT) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_018433.6(KDM3A):c.557-5_557-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 65 hom., cov: 0)

Exomes 𝑓: 0.064 ( 21 hom. )

Consequence

KDM3A
NM_018433.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.593

Variant links:

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]

KDM3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6 link	c.557-5_557-4dupTT		splice_region_variant, intron_variant	Intron 5 of 25	ENST00000312912.10	NP_060903.2	Q9Y4C1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3A	ENST00000312912.10 link	c.557-26_557-25insTT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5		Q9Y4C1

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

2928

AN:

124156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0461

Gnomad AMI

AF:

0.0249

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.0312

Gnomad EAS

AF:

0.00833

Gnomad SAS

AF:

0.00588

Gnomad FIN

AF:

0.0266

Gnomad MID

AF:

0.0197

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.0176

GnomAD3 exomes

AF:

0.0853

AC:

2657

AN:

31146

Hom.:

AF XY:

0.0824

AC XY:

1427

AN XY:

17322

show subpopulations

Gnomad AFR exome

AF:

0.0980

Gnomad AMR exome

AF:

0.0674

Gnomad ASJ exome

AF:

0.0647

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.0586

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0775

Gnomad OTH exome

AF:

0.0802

GnomAD4 exome

AF:

0.0643

AC:

58828

AN:

914520

Hom.:

Cov.:

AF XY:

0.0640

AC XY:

28962

AN XY:

452642

show subpopulations

Gnomad4 AFR exome

AF:

0.0770

Gnomad4 AMR exome

AF:

0.0691

Gnomad4 ASJ exome

AF:

0.0658

Gnomad4 EAS exome

AF:

0.0763

Gnomad4 SAS exome

AF:

0.0690

Gnomad4 FIN exome

AF:

0.0948

Gnomad4 NFE exome

AF:

0.0617

Gnomad4 OTH exome

AF:

0.0659

GnomAD4 genome

AF:

0.0236

AC:

2927

AN:

124140

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1358

AN XY:

58192

show subpopulations

Gnomad4 AFR

AF:

0.0461

Gnomad4 AMR

AF:

0.0168

Gnomad4 ASJ

AF:

0.0312

Gnomad4 EAS

AF:

0.00836

Gnomad4 SAS

AF:

0.00566

Gnomad4 FIN

AF:

0.0266

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.0169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over