NM_004187.5:c.3121-14G>T

Variant names:

• chrX-53195424-C-A
• rs1934763184
• NM_004187.5:c.3121-14G>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.3121-14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,078,501 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom. 1 hem.)
• Consequence: KDM5C NM_004187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• 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]

MIR6895 (HGNC:50210): (microRNA 6895) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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=-0.85).

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.3121-14G>T		intron	N/A	NP_004178.2	P41229-1
	KDM5C	NM_001282622.3		c.3118-14G>T		intron	N/A	NP_001269551.1	P41229-5
	KDM5C	NM_001353978.3		c.3121-14G>T		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.3121-14G>T		intron	N/A	ENSP00000364550.4	P41229-1
	KDM5C	ENST00000404049.7	TSL:1	c.3118-14G>T		intron	N/A	ENSP00000385394.3	P41229-5
	KDM5C	ENST00000935430.1		c.3223-14G>T		intron	N/A	ENSP00000605489.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1078501 Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 1 AN XY: 346715

African (AFR) AF: 0.00 AC: 0 AN: 25990

American (AMR) AF: 0.00 AC: 0 AN: 33970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19053

East Asian (EAS) AF: 0.00 AC: 0 AN: 29625

South Asian (SAS) AF: 0.00 AC: 0 AN: 51843

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39763

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4106

European-Non Finnish (NFE) AF: 0.00000241 AC: 2 AN: 828783

Other (OTH) AF: 0.00 AC: 0 AN: 45368

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.30
PhyloP100		-0.93

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: rs1934763184; hg19: chrX-53224606;