X-53192476-G-A

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.*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

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=-0.49).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.*491C>T		3_prime_UTR_variant	26/26	ENST00000375401.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5C	ENST00000375401.8	c.*491C>T		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 453 AN: 107524 Hom.: 5 Cov.: 21 AF XY: 0.00317 AC XY: 95 AN XY: 30014

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

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.000289

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000952

Gnomad4 OTH exome AF: 0.000956

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

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.00130

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000385

Gnomad4 OTH AF: 0.00208

Alfa AF: 0.000143 Hom.: 1

Bravo AF: 0.00497

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

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	12
Dann	Benign	0.83
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1

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: rs17002644; hg19: chrX-53221658;