Variant 7-140096986-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030647.2(KDM7A):c.2078C>T(p.Thr693Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KDM7A
NM_030647.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10614544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM7A	NM_030647.2 linkuse as main transcript	c.2078C>T	p.Thr693Ile	missense_variant	16/20	ENST00000397560.7	NP_085150.1	Q6ZMT4-1
KDM7A	XM_047420879.1 linkuse as main transcript	c.2078C>T	p.Thr693Ile	missense_variant	16/19		XP_047276835.1
KDM7A	XM_011516587.3 linkuse as main transcript	c.992C>T	p.Thr331Ile	missense_variant	10/14		XP_011514889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM7A	ENST00000397560.7 linkuse as main transcript	c.2078C>T	p.Thr693Ile	missense_variant	16/20	2	NM_030647.2	ENSP00000380692.2		Q6ZMT4-1
KDM7A	ENST00000472616.1 linkuse as main transcript	n.860C>T		non_coding_transcript_exon_variant	8/13	1		ENSP00000420143.1		H9KVD6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459968

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 19, 2022

The c.2078C>T (p.T693I) alteration is located in exon 16 (coding exon 16) of the KDM7A gene. This alteration results from a C to T substitution at nucleotide position 2078, causing the threonine (T) at amino acid position 693 to be replaced by an isoleucine (I). 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

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

0.0090

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.77

M_CAP

Benign

0.0030

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

REVEL

Benign

0.043

Sift

Benign

0.21

Sift4G

Benign

0.20

Polyphen

0.0060

Vest4

0.14

MutPred

0.18

Gain of sheet (P = 0.039);

MVP

0.043

MPC

0.28

ClinPred

0.65

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over