1-43653205-C-T

Variant names:

• chr1-43653205-C-T
• rs140577325
• NM_014663.3:c.30C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_014663.3(KDM4A):​c.30C>T​(p.Pro10Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,612,924 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (16 hom.)
• Consequence: KDM4A NM_014663.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0650
• Publications: 0 publications found

Genes affected

KDM4A (HGNC:22978): (lysine demethylase 4A) This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein containing a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor. [provided by RefSeq, Apr 2009]

ENSG00000284989 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-43653205-C-T is Benign according to our data. Variant chr1-43653205-C-T is described in ClinVar as Benign. ClinVar VariationId is 732098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.065 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00682 (1038/152272) while in subpopulation AFR AF = 0.024 (997/41550). AF 95% confidence interval is 0.0228. There are 19 homozygotes in GnomAd4. There are 516 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1038 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014663.3. 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
	KDM4A	NM_014663.3	MANE Select	c.30C>T	p.Pro10Pro	synonymous	Exon 2 of 22	NP_055478.2	O75164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4A	ENST00000372396.4	TSL:1 MANE Select	c.30C>T	p.Pro10Pro	synonymous	Exon 2 of 22	ENSP00000361473.3	O75164-1
	ENSG00000284989	ENST00000645057.1		n.30C>T		non_coding_transcript_exon	Exon 2 of 26	ENSP00000494063.1	A0A2R8Y4U1
	KDM4A	ENST00000951155.1		c.30C>T	p.Pro10Pro	synonymous	Exon 2 of 23	ENSP00000621214.1

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 1037 AN: 152154 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00168 AC: 421 AN: 250596 AF XY: 0.00125

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.000699

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000623 AC: 910 AN: 1460652 Hom.: 16 Cov.: 30 AF XY: 0.000513 AC XY: 373 AN XY: 726658

African (AFR) AF: 0.0231 AC: 771 AN: 33440

American (AMR) AF: 0.000628 AC: 28 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111382

Other (OTH) AF: 0.00139 AC: 84 AN: 60346

GnomAD4 genome AF: 0.00682 AC: 1038 AN: 152272 Hom.: 19 Cov.: 32 AF XY: 0.00693 AC XY: 516 AN XY: 74464

African (AFR) AF: 0.0240 AC: 997 AN: 41550

American (AMR) AF: 0.00157 AC: 24 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00389 Hom.: 4

Bravo AF: 0.00760

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		-0.065
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs140577325; hg19: chr1-44118876;