rs797044472

chrX-53196962-T-C

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.2705A>G(p.Gln902Arg) 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. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: KDM5C NM_004187.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.04

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 where missense usually causes diseases, KDM5C
• BP4: Computational evidence support a benign effect (MetaRNN=0.15371862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.2705A>G	p.Gln902Arg	missense_variant	19/26	ENST00000375401.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5C	ENST00000375401.8	c.2705A>G	p.Gln902Arg	missense_variant	19/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	18
Dann	Uncertain	0.99
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.54	T;T;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.87	N;N;N;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.0060	.;B;.;.;.
Vest4		0.12
MutPred		0.57		.;Gain of MoRF binding (P = 0.0168);.;Gain of MoRF binding (P = 0.0168);.;
MVP		0.31
MPC		0.59
ClinPred		0.25	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.25
gMVP		0.42

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

Other links and lift over

dbSNP: rs797044472; hg19: chrX-53226144;