chr2-86456416-ATT-A

Variant names:

• chr2-86456416-ATT-A
• rs11431031
• NM_018433.6:c.557-5_557-4delTT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_018433.6(KDM3A):​c.557-5_557-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,044,710 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 0)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: KDM3A NM_018433.6 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.593
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 2-86456416-ATT-A is Benign according to our data. Variant chr2-86456416-ATT-A is described in ClinVar as Benign. ClinVar VariationId is 3038781.Status of the report is no_assertion_criteria_provided, 0 stars.

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.557-5_557-4delTT		splice_region intron	N/A	NP_060903.2
	KDM3A	NM_001146688.2		c.557-5_557-4delTT		splice_region intron	N/A	NP_001140160.1	Q9Y4C1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM3A	ENST00000312912.10	TSL:1 MANE Select	c.557-25_557-24delTT		intron	N/A	ENSP00000323659.5	Q9Y4C1
	KDM3A	ENST00000409064.5	TSL:1	c.557-25_557-24delTT		intron	N/A	ENSP00000386516.1	Q9Y4C1
	KDM3A	ENST00000900202.1		c.557-25_557-24delTT		intron	N/A	ENSP00000570261.1

Frequencies

GnomAD3 genomes AF: 0.0000805 AC: 10 AN: 124186 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000838

Gnomad ASJ AF: 0.000312

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000665

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000818

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0266 AC: 827 AN: 31146 AF XY: 0.0285

Gnomad AFR exome AF: 0.0227

Gnomad AMR exome AF: 0.0428

Gnomad ASJ exome AF: 0.0336

Gnomad EAS exome AF: 0.0160

Gnomad FIN exome AF: 0.00605

Gnomad NFE exome AF: 0.0271

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0154 AC: 14132 AN: 920540 Hom.: 0 AF XY: 0.0159 AC XY: 7218 AN XY: 455286

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

African (AFR) AF: 0.0148 AC: 267 AN: 18076

American (AMR) AF: 0.0272 AC: 301 AN: 11072

Ashkenazi Jewish (ASJ) AF: 0.0206 AC: 308 AN: 14972

East Asian (EAS) AF: 0.00993 AC: 236 AN: 23764

South Asian (SAS) AF: 0.0289 AC: 1232 AN: 42692

European-Finnish (FIN) AF: 0.0142 AC: 503 AN: 35492

Middle Eastern (MID) AF: 0.0232 AC: 61 AN: 2628

European-Non Finnish (NFE) AF: 0.0144 AC: 10590 AN: 733988

Other (OTH) AF: 0.0167 AC: 634 AN: 37856

⚠️ 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.

GnomAD4 genome AF: 0.0000805 AC: 10 AN: 124170 Hom.: 0 Cov.: 0 AF XY: 0.0000687 AC XY: 4 AN XY: 58212

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

African (AFR) AF: 0.00 AC: 0 AN: 32464

American (AMR) AF: 0.0000837 AC: 1 AN: 11952

Ashkenazi Jewish (ASJ) AF: 0.000312 AC: 1 AN: 3204

East Asian (EAS) AF: 0.00 AC: 0 AN: 4314

South Asian (SAS) AF: 0.00 AC: 0 AN: 3888

European-Finnish (FIN) AF: 0.000665 AC: 3 AN: 4510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.0000818 AC: 5 AN: 61112

Other (OTH) AF: 0.00 AC: 0 AN: 1652

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000509225), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1296

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KDM3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11431031; hg19: chr2-86683539;