X-53214675-T-C

Variant names:

• chrX-53214675-T-C
• rs1556850730
• NM_004187.5:c.1122+14A>G

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.1122+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000906 in 110,381 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 𝑓 0.0000091 (0 hom., 1 hem., cov: 23)
• Consequence: KDM5C NM_004187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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-IT1 (HGNC:41384): (KDM5C intronic transcript 1)

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=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004187.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5C	NM_004187.5	MANE Select	c.1122+14A>G		intron	N/A	NP_004178.2	P41229-1
	KDM5C	NM_001282622.3		c.1119+14A>G		intron	N/A	NP_001269551.1	P41229-5
	KDM5C	NM_001353978.3		c.1122+14A>G		intron	N/A	NP_001340907.1	P41229-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5C	ENST00000375401.8	TSL:1 MANE Select	c.1122+14A>G		intron	N/A	ENSP00000364550.4	P41229-1
	KDM5C	ENST00000404049.7	TSL:1	c.1119+14A>G		intron	N/A	ENSP00000385394.3	P41229-5
	KDM5C	ENST00000935430.1		c.1224+14A>G		intron	N/A	ENSP00000605489.1

Frequencies

GnomAD3 genomes AF: 0.00000906 AC: 1 AN: 110381 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000906 AC: 1 AN: 110381 Hom.: 0 Cov.: 23 AF XY: 0.0000305 AC XY: 1 AN XY: 32793

African (AFR) AF: 0.0000331 AC: 1 AN: 30200

American (AMR) AF: 0.00 AC: 0 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3503

South Asian (SAS) AF: 0.00 AC: 0 AN: 2579

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52752

Other (OTH) AF: 0.00 AC: 0 AN: 1484

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1556850730; hg19: chrX-53243857;