2-86456416-ATTTTTTTTTTTT-ATTTTTTTTTTT

Variant names:

• chr2-86456416-AT-A
• rs11431031
• NM_018433.6:c.557-4delT

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
• Clinical Significance: Not reported in ClinVar
• 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 -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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 3 Cov.: 0

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

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.: 2 Cov.: 0 AF XY: 0.101 AC XY: 45665 AN XY: 451178

⚠️ 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.

GnomAD4 genome AF: 0.00701 AC: 870 AN: 124186 Hom.: 3 Cov.: 0 AF XY: 0.00764 AC XY: 445 AN XY: 58226

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: 2 AN: 3206

East Asian (EAS) AF: 0.000695 AC: 3 AN: 4314

South Asian (SAS) AF: 0.0116 AC: 45 AN: 3886

European-Finnish (FIN) AF: 0.0175 AC: 79 AN: 4512

Middle Eastern (MID) AF: 0.00435 AC: 1 AN: 230

European-Non Finnish (NFE) AF: 0.00777 AC: 475 AN: 61120

Other (OTH) AF: 0.00726 AC: 12 AN: 1652

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

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; COSMIC: COSV57226455; COSMIC: COSV57226455;