7-140094079-C-G

Variant summary

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

The NM_030647.2(KDM7A):ā€‹c.2434G>Cā€‹(p.Asp812His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,594,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

KDM7A
NM_030647.2 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20
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]

Genome browser will be placed here

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=0.15797201).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KDM7ANM_030647.2 linkuse as main transcriptc.2434G>C p.Asp812His missense_variant 18/20 ENST00000397560.7 NP_085150.1 Q6ZMT4-1
KDM7AXM_047420879.1 linkuse as main transcriptc.2434G>C p.Asp812His missense_variant 18/19 XP_047276835.1
KDM7AXM_011516587.3 linkuse as main transcriptc.1348G>C p.Asp450His missense_variant 12/14 XP_011514889.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KDM7AENST00000397560.7 linkuse as main transcriptc.2434G>C p.Asp812His missense_variant 18/202 NM_030647.2 ENSP00000380692.2 Q6ZMT4-1
KDM7AENST00000472616.1 linkuse as main transcriptn.*98G>C non_coding_transcript_exon_variant 11/131 ENSP00000420143.1 H9KVD6
KDM7AENST00000472616.1 linkuse as main transcriptn.*98G>C 3_prime_UTR_variant 11/131 ENSP00000420143.1 H9KVD6

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000321
AC:
8
AN:
249448
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135332
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1441900
Hom.:
0
Cov.:
26
AF XY:
0.0000167
AC XY:
12
AN XY:
718814
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
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:
0.00000640
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152254
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000248
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJun 19, 2024The c.2434G>C (p.D812H) alteration is located in exon 18 (coding exon 18) of the KDM7A gene. This alteration results from a G to C substitution at nucleotide position 2434, causing the aspartic acid (D) at amino acid position 812 to be replaced by a histidine (H). 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
-0.30
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.033
T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.083
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.012
D
Polyphen
0.93
P
Vest4
0.28
MutPred
0.21
Gain of helix (P = 0.027);
MVP
0.093
MPC
0.70
ClinPred
0.14
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.27

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.

Other links and lift over

dbSNP: rs769521795; hg19: chr7-139793879; COSMIC: COSV50092106; COSMIC: COSV50092106; API