rs139569882

Variant names:

• chrX-53193013-C-G
• NM_004187.5:c.4637G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-53193013-C-G
• chrX-53193013-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_004187.5(KDM5C):​c.4637G>C​(p.Arg1546Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 20)
• Consequence: KDM5C NM_004187.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the KDM5C gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 36 curated pathogenic missense variants (we use a threshold of 10). The gene has 40 curated benign missense variants. Gene score misZ: 5.1452 (above the threshold of 3.09). GenCC associations: The gene is linked to X-linked syndromic intellectual disability, syndromic X-linked intellectual disability Claes-Jensen type.
• BP4: Computational evidence support a benign effect (MetaRNN=0.25157085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5C	NM_004187.5	c.4637G>C	p.Arg1546Pro	missense_variant	Exon 26 of 26	ENST00000375401.8	NP_004178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000375401.8	c.4637G>C	p.Arg1546Pro	missense_variant	Exon 26 of 26	1	NM_004187.5	ENSP00000364550.4

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;.;.
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.55	N;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.90	N;N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.063	B;.;.;.
Vest4		0.44
MutPred		0.19		Gain of glycosylation at R1546 (P = 0.0237);.;.;.;
MVP		0.82
MPC		0.83
ClinPred		0.14	T
GERP RS		0.044
Varity_R		0.21
gMVP		0.36

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: chrX-53222195;