Genetic Variant NM_018433.6:c.557-4delT (chr2-86456416-AT-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018433.6(KDM3A):c.557-4delT 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. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.0070 ( 3 hom., cov: 0)

Exomes 𝑓: 0.099 ( 2 hom. )

Consequence

KDM3A
NM_018433.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.593

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 870 AD gene.

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.557-4delT		splice_region intron	N/A	NP_060903.2
	KDM3A	NM_001146688.2		c.557-4delT		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.557-25delT	intron	N/A	ENSP00000323659.5	Q9Y4C1
KDM3A	ENST00000409064.5	TSL:1	c.557-25delT	intron	N/A	ENSP00000386516.1	Q9Y4C1
KDM3A	ENST00000900202.1		c.557-25delT	intron	N/A	ENSP00000570261.1

Frequencies

GnomAD3 genomes

AF:

0.00700

AC:

869

AN:

124202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.000624

Gnomad EAS

AF:

0.000693

Gnomad SAS

AF:

0.0115

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00394

Gnomad NFE

AF:

0.00777

Gnomad OTH

AF:

0.00727

GnomAD2 exomes

AF:

0.145

AC:

4509

AN:

31146

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0900

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.0987

AC:

89957

AN:

911854

Hom.:

Cov.:

AF XY:

0.101

AC XY:

45665

AN XY:

451178

show subpopulations

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

African (AFR)

AF:

0.0986

AC:

1765

AN:

17902

American (AMR)

AF:

0.125

AC:

1382

AN:

11040

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

1795

AN:

14858

East Asian (EAS)

AF:

0.0717

AC:

1675

AN:

23352

South Asian (SAS)

AF:

0.142

AC:

6040

AN:

42512

European-Finnish (FIN)

AF:

0.0843

AC:

2964

AN:

35152

Middle Eastern (MID)

AF:

0.108

AC:

281

AN:

2594

European-Non Finnish (NFE)

AF:

0.0965

AC:

70172

AN:

726902

Other (OTH)

AF:

0.103

AC:

3883

AN:

37542

⚠️ 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: 0.323

Heterozygous variant carriers

5942

11884

17826

23768

29710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2584

5168

7752

10336

12920

<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:

0.00701

AC:

870

AN:

124186

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

445

AN XY:

58226

show subpopulations

African (AFR)

AF:

0.00471

AC:

153

AN:

32468

American (AMR)

AF:

0.00837

AC:

100

AN:

11954

Ashkenazi Jewish (ASJ)

AF:

0.000624

AC:

AN:

3206

East Asian (EAS)

AF:

0.000695

AC:

AN:

4314

South Asian (SAS)

AF:

0.0116

AC:

AN:

3886

European-Finnish (FIN)

AF:

0.0175

AC:

AN:

4512

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00777

AC:

475

AN:

61120

Other (OTH)

AF:

0.00726

AC:

AN:

1652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

0.59

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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