rs193921056

Variant names:

• chr2-86482107-GTGTT-G
• rs193921056
• NM_018433.6:c.2685+14_2685+17delTGTT

Your query was ambiguous. Multiple possible variants found:

• chr2-86482107-GTGTT-G
• chr2-86482107-GTGTT-GTGTTTGTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000312912.10(KDM3A):​c.2685+6_2685+9delTGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,612,470 control chromosomes in the GnomAD database, including 4,896 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.073 (439 hom., cov: 31)
  • Exomes 𝑓: 0.075 (4457 hom.)
• Consequence: KDM3A ENST00000312912.10 splice_region, intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.00100
• Publications: 4 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000312912.10. 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.2685+14_2685+17delTGTT		intron	N/A	NP_060903.2
	KDM3A	NM_001146688.2		c.2685+14_2685+17delTGTT		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.2685+6_2685+9delTGTT		splice_region intron	N/A	ENSP00000323659.5	Q9Y4C1
	KDM3A	ENST00000409064.5	TSL:1	c.2685+6_2685+9delTGTT		splice_region intron	N/A	ENSP00000386516.1	Q9Y4C1
	KDM3A	ENST00000900202.1		c.2739+6_2739+9delTGTT		splice_region intron	N/A	ENSP00000570261.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11045 AN: 152148 Hom.: 439 Cov.: 31

Gnomad AFR AF: 0.0716

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0573

GnomAD2 exomes AF: 0.0649 AC: 16304 AN: 251078 AF XY: 0.0660

Gnomad AFR exome AF: 0.0697

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.0304

Gnomad EAS exome AF: 0.00903

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.0786

Gnomad OTH exome AF: 0.0652

GnomAD4 exome AF: 0.0751 AC: 109617 AN: 1460204 Hom.: 4457 AF XY: 0.0743 AC XY: 53956 AN XY: 726530

African (AFR) AF: 0.0701 AC: 2345 AN: 33430

American (AMR) AF: 0.0379 AC: 1695 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 836 AN: 26122

East Asian (EAS) AF: 0.0204 AC: 808 AN: 39686

South Asian (SAS) AF: 0.0504 AC: 4341 AN: 86194

European-Finnish (FIN) AF: 0.123 AC: 6591 AN: 53418

Middle Eastern (MID) AF: 0.0621 AC: 358 AN: 5766

European-Non Finnish (NFE) AF: 0.0795 AC: 88294 AN: 1110572

Other (OTH) AF: 0.0721 AC: 4349 AN: 60334

GnomAD4 genome AF: 0.0726 AC: 11052 AN: 152266 Hom.: 439 Cov.: 31 AF XY: 0.0734 AC XY: 5467 AN XY: 74458

African (AFR) AF: 0.0715 AC: 2969 AN: 41546

American (AMR) AF: 0.0559 AC: 855 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3472

East Asian (EAS) AF: 0.00984 AC: 51 AN: 5182

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4832

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5367 AN: 68008

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0431 Hom.: 41

Bravo AF: 0.0672

Asia WGS AF: 0.0370 AC: 130 AN: 3478

EpiCase AF: 0.0757

EpiControl AF: 0.0771

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0010
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193921056;

hg19: chr2-86709230;