Genetic Variant KDM3A:c.557-7_557-4delTTTT (chr2-86456416-ATTTT-A) – 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_557-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,057,058 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: 0.00022 ( 0 hom. )

Consequence

KDM3A
NM_018433.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

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 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6 link	c.557-7_557-4delTTTT		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.557-25_557-22delTTTT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5		Q9Y4C1

Frequencies

GnomAD3 genomes

AF:

0.00000805

AC:

AN:

124200

Hom.:

Cov.:

show subpopulations

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

GnomAD4 exome

AF:

0.000223

AC:

208

AN:

932858

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

461788

show subpopulations

Gnomad4 AFR exome

AF:

0.000273

Gnomad4 AMR exome

AF:

0.000354

Gnomad4 ASJ exome

AF:

0.000263

Gnomad4 EAS exome

AF:

0.0000833

Gnomad4 SAS exome

AF:

0.000323

Gnomad4 FIN exome

AF:

0.000279

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.000260

GnomAD4 genome

AF:

0.00000805

AC:

AN:

124200

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

58218

show subpopulations

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

Name

Calibrated prediction

Score

Prediction

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

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