rs17002644

Variant names:

• chrX-53192476-G-A
• rs17002644
• NM_004187.5:c.*491C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-53192476-G-A
• chrX-53192476-G-T

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.*491C>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 0.00194 in 278,737 control chromosomes in the GnomAD database, including 5 homozygotes. There are 124 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., 96 hem., cov: 21)
  • Exomes 𝑓: 0.00050 (0 hom. 28 hem.)
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.859
• Publications: 1 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=-0.49).
• BP6: Variant X-53192476-G-A is Benign according to our data. Variant chrX-53192476-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1181456.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00424 (456/107569) while in subpopulation AFR AF = 0.0149 (438/29420). AF 95% confidence interval is 0.0137. There are 5 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.*491C>T		3_prime_UTR	Exon 26 of 26	NP_004178.2	P41229-1
	KDM5C	NM_001282622.3		c.*491C>T		3_prime_UTR	Exon 26 of 26	NP_001269551.1	P41229-5
	KDM5C	NM_001353978.3		c.*491C>T		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.*491C>T		3_prime_UTR	Exon 26 of 26	ENSP00000364550.4	P41229-1
	KDM5C	ENST00000404049.7	TSL:1	c.*491C>T		3_prime_UTR	Exon 26 of 26	ENSP00000385394.3	P41229-5
	KDM5C	ENST00000691505.1		c.4319C>T	p.Thr1440Ile	missense	Exon 26 of 26	ENSP00000510354.1	A0A8I5KXH7

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 453 AN: 107524 Hom.: 5 Cov.: 21

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.0000384

Gnomad OTH AF: 0.00211

GnomAD4 exome AF: 0.000502 AC: 86 AN: 171168 Hom.: 0 Cov.: 0 AF XY: 0.000650 AC XY: 28 AN XY: 43056

African (AFR) AF: 0.0124 AC: 72 AN: 5801

American (AMR) AF: 0.000289 AC: 2 AN: 6917

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6119

East Asian (EAS) AF: 0.00 AC: 0 AN: 15728

South Asian (SAS) AF: 0.00 AC: 0 AN: 4553

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14715

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 795

European-Non Finnish (NFE) AF: 0.00000952 AC: 1 AN: 105028

Other (OTH) AF: 0.000956 AC: 11 AN: 11512

GnomAD4 genome AF: 0.00424 AC: 456 AN: 107569 Hom.: 5 Cov.: 21 AF XY: 0.00319 AC XY: 96 AN XY: 30069

African (AFR) AF: 0.0149 AC: 438 AN: 29420

American (AMR) AF: 0.00130 AC: 13 AN: 9966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2614

East Asian (EAS) AF: 0.00 AC: 0 AN: 3361

South Asian (SAS) AF: 0.00 AC: 0 AN: 2369

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.0000385 AC: 2 AN: 52013

Other (OTH) AF: 0.00208 AC: 3 AN: 1443

Alfa AF: 0.000143 Hom.: 1

Bravo AF: 0.00497

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	-0.49
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.86
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
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: rs17002644; hg19: chrX-53221658;