7-140097556-A-T

Position:

• chr7-140097556-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030647.2(KDM7A):​c.2005T>A​(p.Cys669Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.10

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27009097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM7A	NM_030647.2	c.2005T>A	p.Cys669Ser	missense_variant	15/20	ENST00000397560.7	NP_085150.1
KDM7A	XM_047420879.1	c.2005T>A	p.Cys669Ser	missense_variant	15/19		XP_047276835.1
KDM7A	XM_011516587.3	c.919T>A	p.Cys307Ser	missense_variant	9/14		XP_011514889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM7A	ENST00000397560.7	c.2005T>A	p.Cys669Ser	missense_variant	15/20	2	NM_030647.2	ENSP00000380692	P1
KDM7A	ENST00000472616.1	c.790T>A	p.Cys264Ser	missense_variant, NMD_transcript_variant	7/13	1		ENSP00000420143

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

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

Jan 03, 2022

The c.2005T>A (p.C669S) alteration is located in exon 15 (coding exon 15) of the KDM7A gene. This alteration results from a T to A substitution at nucleotide position 2005, causing the cysteine (C) at amino acid position 669 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.82
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.095
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.18
Sift	Benign	0.80	T
Sift4G	Benign	0.74	T
Polyphen		0.013	B
Vest4		0.61
MutPred		0.18		Gain of phosphorylation at C669 (P = 0.0047);
MVP		0.52
MPC		0.32
ClinPred		0.37	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-139797356;