Variant 7-140091946-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030647.2(KDM7A):c.2589C>G(p.Asn863Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

KDM7A
NM_030647.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

KDM7A (HGNC:22224): (lysine demethylase 7A) Enables histone demethylase activity; methylated histone binding activity; and transition metal ion binding activity. Involved in histone lysine demethylation. Located in nucleolus and nucleoplasm. Implicated in melanoma. [provided by Alliance of Genome Resources, Apr 2022]

KDM7A links:

KDM7A (HGNC:):

KDM7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023846716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM7A	NM_030647.2 linkuse as main transcript	c.2589C>G	p.Asn863Lys	missense_variant	19/20	ENST00000397560.7	NP_085150.1	Q6ZMT4-1
KDM7A	XM_011516587.3 linkuse as main transcript	c.1503C>G	p.Asn501Lys	missense_variant	13/14		XP_011514889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDM7A	ENST00000397560.7 linkuse as main transcript	c.2589C>G	p.Asn863Lys	missense_variant	19/20	2	NM_030647.2	ENSP00000380692.2	Q6ZMT4-1
KDM7A	ENST00000472616.1 linkuse as main transcript	n.*253C>G		non_coding_transcript_exon_variant	12/13	1		ENSP00000420143.1	H9KVD6
KDM7A	ENST00000472616.1 linkuse as main transcript	n.*253C>G		3_prime_UTR_variant	12/13	1		ENSP00000420143.1	H9KVD6
KDM7A	ENST00000478996.1 linkuse as main transcript	n.196C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

249476

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000184

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000232

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.2589C>G (p.N863K) alteration is located in exon 19 (coding exon 19) of the KDM7A gene. This alteration results from a C to G substitution at nucleotide position 2589, causing the asparagine (N) at amino acid position 863 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.65

M_CAP

Benign

0.011

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.32

REVEL

Benign

0.055

Sift

Benign

0.032

Sift4G

Benign

0.89

Polyphen

0.0050

Vest4

0.081

MutPred

0.21

Gain of ubiquitination at N863 (P = 0.0066);

MVP

0.043

MPC

0.30

ClinPred

0.015

GERP RS

3.0

Varity_R

0.096

gMVP

0.10

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over