chrX-53191607-T-C

Variant names:

• chrX-53191607-T-C
• NM_001353984.2:c.4324A>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001353984.2(KDM5C):​c.4324A>G​(p.Asn1442Asp) 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. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: KDM5C NM_001353984.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

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 Likely_benign. 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 (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5C	NM_001353984.2	c.4324A>G	p.Asn1442Asp	missense_variant	Exon 26 of 26		NP_001340913.1
KDM5C	NM_001353979.2	c.4314+1830A>G		intron_variant	Intron 25 of 25		NP_001340908.1
KDM5C	NM_001353981.2	c.4308+1830A>G		intron_variant	Intron 25 of 25		NP_001340910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000688699.1	c.4324A>G	p.Asn1442Asp	missense_variant	Exon 26 of 26			ENSP00000510430.1
KDM5C	ENST00000452825	c.*1137A>G		3_prime_UTR_variant	Exon 24 of 24	5		ENSP00000445176.1
KDM5C	ENST00000685641.1	c.4308+1830A>G		intron_variant	Intron 25 of 25			ENSP00000509818.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KDM5C: PM2, PP2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.86

Splicing

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-53220789;