NM_004187.5:c.*94C>G

Variant names:

• chrX-53192873-G-C
• rs782275907
• NM_004187.5:c.*94C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004187.5(KDM5C):​c.*94C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.12 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280
• 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, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-53192873-G-C is Benign according to our data. Variant chrX-53192873-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1215665.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*94C>G		3_prime_UTR	Exon 26 of 26	NP_004178.2	P41229-1
	KDM5C	NM_001282622.3		c.*94C>G		3_prime_UTR	Exon 26 of 26	NP_001269551.1	P41229-5
	KDM5C	NM_001353978.3		c.*94C>G		3_prime_UTR	Exon 26 of 26	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.*94C>G		3_prime_UTR	Exon 26 of 26	ENSP00000364550.4	P41229-1
	KDM5C	ENST00000404049.7	TSL:1	c.*94C>G		3_prime_UTR	Exon 26 of 26	ENSP00000385394.3	P41229-5
	KDM5C	ENST00000935430.1		c.*94C>G		3_prime_UTR	Exon 27 of 27	ENSP00000605489.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 2031 AN: 19635 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0933

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.0147 AC: 740 AN: 50393 AF XY: 0.00

Gnomad AFR exome AF: 0.00876

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.0142

Gnomad FIN exome AF: 0.00170

Gnomad NFE exome AF: 0.0209

Gnomad OTH exome AF: 0.0123

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.119 AC: 17673 AN: 148476 Hom.: 0 Cov.: 5 AF XY: 0.0000363 AC XY: 1 AN XY: 27574

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0710 AC: 264 AN: 3716

American (AMR) AF: 0.0532 AC: 342 AN: 6427

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 268 AN: 3498

East Asian (EAS) AF: 0.0655 AC: 349 AN: 5328

South Asian (SAS) AF: 0.0756 AC: 692 AN: 9156

European-Finnish (FIN) AF: 0.0488 AC: 640 AN: 13125

Middle Eastern (MID) AF: 0.0569 AC: 46 AN: 808

European-Non Finnish (NFE) AF: 0.142 AC: 14222 AN: 100222

Other (OTH) AF: 0.137 AC: 850 AN: 6196

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.103 AC: 2030 AN: 19656 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2722

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0776 AC: 440 AN: 5669

American (AMR) AF: 0.0766 AC: 152 AN: 1984

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 52 AN: 480

East Asian (EAS) AF: 0.0703 AC: 26 AN: 370

South Asian (SAS) AF: 0.0558 AC: 13 AN: 233

European-Finnish (FIN) AF: 0.132 AC: 94 AN: 713

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.123 AC: 1209 AN: 9805

Other (OTH) AF: 0.123 AC: 37 AN: 301

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.84
DANN	Benign	0.70
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism

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: rs782275907; hg19: chrX-53222055;