chr2-86456416-ATT-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

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. 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

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

Verdict is Benign. Variant got -9 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 id is 3038781.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0154 (14132/920540) while in subpopulation SAS AF= 0.0289 (1232/42692). AF 95% confidence interval is 0.0275. There are 0 homozygotes in gnomad4_exome. There are 7218 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6	c.557-5_557-4delTT		splice_region_variant, intron_variant	Intron 5 of 25	ENST00000312912.10	NP_060903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3A	ENST00000312912.10	c.557-25_557-24delTT		intron_variant	Intron 5 of 25	1	NM_018433.6	ENSP00000323659.5

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

GnomAD3 exomes AF: 0.0266 AC: 827 AN: 31146 Hom.: 0 AF XY: 0.0285 AC XY: 494 AN XY: 17322

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 SAS exome AF: 0.0504

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

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.0272

Gnomad4 ASJ exome AF: 0.0206

Gnomad4 EAS exome AF: 0.00993

Gnomad4 SAS exome AF: 0.0289

Gnomad4 FIN exome AF: 0.0142

Gnomad4 NFE exome AF: 0.0144

Gnomad4 OTH exome AF: 0.0167

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000837

Gnomad4 ASJ AF: 0.000312

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000665

Gnomad4 NFE AF: 0.0000818

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KDM3A-related disorder Benign:1

Mar 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11431031; hg19: chr2-86683539;