Genetic Variant KDM3A:c.557-8_557-4delTTTTT (chr2-86456416-ATTTTT-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018433.6(KDM3A):c.557-8_557-4delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,057,686 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

KDM3A
NM_018433.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018433.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM3A	NM_018433.6	MANE Select	c.557-8_557-4delTTTTT		splice_region intron	N/A	NP_060903.2
	KDM3A	NM_001146688.2		c.557-8_557-4delTTTTT		splice_region intron	N/A	NP_001140160.1	Q9Y4C1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM3A	ENST00000312912.10	TSL:1 MANE Select	c.557-25_557-21delTTTTT	intron	N/A	ENSP00000323659.5	Q9Y4C1
KDM3A	ENST00000409064.5	TSL:1	c.557-25_557-21delTTTTT	intron	N/A	ENSP00000386516.1	Q9Y4C1
KDM3A	ENST00000900202.1		c.557-25_557-21delTTTTT	intron	N/A	ENSP00000570261.1

Frequencies

GnomAD3 genomes

AF:

0.0000161

AC:

AN:

124204

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000386

AC:

AN:

933482

Hom.:

AF XY:

0.0000454

AC XY:

AN XY:

462082

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

18304

American (AMR)

AF:

0.0000886

AC:

AN:

11288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15224

East Asian (EAS)

AF:

0.000125

AC:

AN:

24038

South Asian (SAS)

AF:

0.0000691

AC:

AN:

43434

European-Finnish (FIN)

AF:

0.0000279

AC:

AN:

35872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2664

European-Non Finnish (NFE)

AF:

0.0000363

AC:

AN:

744196

Other (OTH)

AF:

0.0000260

AC:

AN:

38462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.281

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000161

AC:

AN:

124204

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

58220

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32430

American (AMR)

AF:

0.0000838

AC:

AN:

11936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3206

East Asian (EAS)

AF:

0.00

AC:

AN:

4330

South Asian (SAS)

AF:

0.00

AC:

AN:

3914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61128

Other (OTH)

AF:

0.00

AC:

AN:

1650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

1296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over