7-140096647-C-T

Position:

• chr7-140096647-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030647.2(KDM7A):​c.2282G>A​(p.Gly761Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM7A NM_030647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.108

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]

ACMG classification

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=0.03995037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM7A	NM_030647.2	c.2282G>A	p.Gly761Asp	missense_variant	17/20	ENST00000397560.7	NP_085150.1
KDM7A	XM_047420879.1	c.2282G>A	p.Gly761Asp	missense_variant	17/19		XP_047276835.1
KDM7A	XM_011516587.3	c.1196G>A	p.Gly399Asp	missense_variant	11/14		XP_011514889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM7A	ENST00000397560.7	c.2282G>A	p.Gly761Asp	missense_variant	17/20	2	NM_030647.2	ENSP00000380692	P1
KDM7A	ENST00000472616.1	c.1067G>A	p.Gly356Asp	missense_variant, NMD_transcript_variant	9/13	1		ENSP00000420143

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.2282G>A (p.G761D) alteration is located in exon 17 (coding exon 17) of the KDM7A gene. This alteration results from a G to A substitution at nucleotide position 2282, causing the glycine (G) at amino acid position 761 to be replaced by an aspartic acid (D). 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	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.5
DANN	Benign	0.84
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.050
Sift	Benign	0.24	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.11		Gain of helix (P = 0.0854);
MVP		0.12
MPC		0.33
ClinPred		0.026	T
GERP RS		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.087
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-139796447;