X-53192587-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 61 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.*380G>A		3_prime_UTR_variant	26/26	ENST00000375401.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5C	ENST00000375401.8	c.*380G>A		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 157 AN: 109011 Hom.: 1 Cov.: 20 AF XY: 0.00195 AC XY: 61 AN XY: 31337

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

Gnomad4 AFR exome AF: 0.0000800

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.000755

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

Gnomad4 AFR AF: 0.000134

Gnomad4 AMR AF: 0.0000969

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.00130

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00162 Hom.: 9

Bravo AF: 0.000574

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	14
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs782663215; hg19: chrX-53221769;