chrX-53192587-C-T

Variant names:

• chrX-53192587-C-T
• rs782663215
• NM_004187.5:c.*380G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004187.5(KDM5C):​c.*380G>A 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 0.0014 (1 hom., 61 hem., cov: 20)
  • Exomes 𝑓: 0.0021 (2 hom. 241 hem.)
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.652
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-53192587-C-T is Benign according to our data. Variant chrX-53192587-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1219148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00144 (157/109065) while in subpopulation NFE AF = 0.0013 (68/52261). AF 95% confidence interval is 0.00105. There are 1 homozygotes in GnomAd4. There are 61 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 61 XL gene

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.*380G>A		3_prime_UTR	Exon 26 of 26	NP_004178.2	P41229-1
	KDM5C	NM_001282622.3		c.*380G>A		3_prime_UTR	Exon 26 of 26	NP_001269551.1	P41229-5
	KDM5C	NM_001353978.3		c.*380G>A		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.*380G>A		3_prime_UTR	Exon 26 of 26	ENSP00000364550.4	P41229-1
	KDM5C	ENST00000404049.7	TSL:1	c.*380G>A		3_prime_UTR	Exon 26 of 26	ENSP00000385394.3	P41229-5
	KDM5C	ENST00000935430.1		c.*380G>A		3_prime_UTR	Exon 27 of 27	ENSP00000605489.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 157 AN: 109011 Hom.: 1 Cov.: 20

Gnomad AFR AF: 0.000134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000970

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00130

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00207 AC: 868 AN: 419740 Hom.: 2 Cov.: 6 AF XY: 0.00205 AC XY: 241 AN XY: 117394

African (AFR) AF: 0.0000800 AC: 1 AN: 12503

American (AMR) AF: 0.00 AC: 0 AN: 22351

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11311

East Asian (EAS) AF: 0.00 AC: 0 AN: 22884

South Asian (SAS) AF: 0.00 AC: 0 AN: 25964

European-Finnish (FIN) AF: 0.0164 AC: 525 AN: 31999

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1587

European-Non Finnish (NFE) AF: 0.00121 AC: 325 AN: 268610

Other (OTH) AF: 0.000755 AC: 17 AN: 22531

GnomAD4 genome AF: 0.00144 AC: 157 AN: 109065 Hom.: 1 Cov.: 20 AF XY: 0.00194 AC XY: 61 AN XY: 31401

African (AFR) AF: 0.000134 AC: 4 AN: 29874

American (AMR) AF: 0.0000969 AC: 1 AN: 10318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2615

East Asian (EAS) AF: 0.00 AC: 0 AN: 3392

South Asian (SAS) AF: 0.00 AC: 0 AN: 2483

European-Finnish (FIN) AF: 0.0146 AC: 84 AN: 5756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.00130 AC: 68 AN: 52261

Other (OTH) AF: 0.00 AC: 0 AN: 1493

Alfa AF: 0.00162 Hom.: 9

Bravo AF: 0.000574

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	-0.48
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs782663215; hg19: chrX-53221769;