chrX-53195968-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5

The NM_004187.5(KDM5C):​c.3068A>T​(p.Lys1023Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1023R) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 24)

Consequence

KDM5C
NM_004187.5 missense

Scores

2
9
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.25

Publications

0 publications found
Variant links:
Genes affected
KDM5C (HGNC:11114): (lysine demethylase 5C) This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. Mutations in this gene have been associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]
KDM5C Gene-Disease associations (from GenCC):
  • syndromic X-linked intellectual disability Claes-Jensen type
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • X-linked syndromic intellectual disability
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chrX-53195968-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 254201.We mark this variant Likely_pathogenic, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM5CNM_004187.5 linkc.3068A>T p.Lys1023Met missense_variant Exon 20 of 26 ENST00000375401.8 NP_004178.2 P41229-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM5CENST00000375401.8 linkc.3068A>T p.Lys1023Met missense_variant Exon 20 of 26 1 NM_004187.5 ENSP00000364550.4 P41229-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
.;T;.;.;.
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.57
D;D;D;D;D
MetaSVM
Benign
-0.42
T
MutationAssessor
Pathogenic
3.0
.;M;.;M;.
PhyloP100
3.3
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.6
D;D;D;D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D
Polyphen
0.23
.;B;.;.;.
Vest4
0.48
MutPred
0.60
.;Loss of ubiquitination at K1023 (P = 0.0446);.;Loss of ubiquitination at K1023 (P = 0.0446);.;
MVP
0.58
MPC
1.7
ClinPred
0.99
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.75
gMVP
0.81
Mutation Taster
=76/24
polymorphism

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

Other links and lift over

dbSNP: rs782367133; hg19: chrX-53225150; API