Genetic Variant KDM3A:c.557-7_557-4dupTTTT (chr2-86456416-A-ATTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_018433.6(KDM3A):c.557-7_557-4dupTTTT 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 0.000024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00064 ( 0 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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 595 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6 link	c.557-7_557-4dupTTTT		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_557-25insTTTT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5		Q9Y4C1

Frequencies

GnomAD3 genomes

AF:

0.0000242

AC:

AN:

124184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000838

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

GnomAD4 exome

AF:

0.000638

AC:

595

AN:

932712

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

307

AN XY:

461732

show subpopulations

Gnomad4 AFR exome

AF:

0.000875

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.000791

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.0000242

AC:

AN:

124168

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

58214

show subpopulations

Gnomad4 AFR

AF:

0.0000308

Gnomad4 AMR

AF:

0.0000837

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

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.

2-86456416-ATTTTTTTTTT-ATTTTTTTTTTTTTT

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