rs781971436

Variant names:

• chrX-53192924-C-A
• rs781971436
• NM_004187.5:c.*43G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-53192924-C-A
• chrX-53192924-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004187.5(KDM5C):​c.*43G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 863,646 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: 16)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5C	NM_004187.5	c.*43G>T		3_prime_UTR_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.*43G>T		3_prime_UTR_variant	Exon 26 of 26	1	NM_004187.5	ENSP00000364550.4

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 863646 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 270278

African (AFR) AF: 0.00 AC: 0 AN: 19537

American (AMR) AF: 0.00 AC: 0 AN: 18136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9221

East Asian (EAS) AF: 0.00 AC: 0 AN: 14855

South Asian (SAS) AF: 0.00 AC: 0 AN: 42036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2889

European-Non Finnish (NFE) AF: 0.00000143 AC: 1 AN: 700697

Other (OTH) AF: 0.00 AC: 0 AN: 31887

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs781971436; hg19: chrX-53222106;