X-53192881-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.*86G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000588 in 1,052,812 control chromosomes in the GnomAD database, including 5 homozygotes. There are 107 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 0.0033 (4 hom., 37 hem., cov: 17)
  • Exomes 𝑓: 0.00032 (1 hom. 70 hem.)
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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=-0.53).
• BP6: Variant X-53192881-C-T is Benign according to our data. Variant chrX-53192881-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00332 (316/95136) while in subpopulation AFR AF= 0.0117 (307/26143). AF 95% confidence interval is 0.0107. There are 4 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 17. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.*86G>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.*86G>A		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 315 AN: 95098 Hom.: 4 Cov.: 17 AF XY: 0.00182 AC XY: 37 AN XY: 20310

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000553

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: 0.0000429

Gnomad OTH AF: 0.00161

GnomAD3 exomes AF: 0.00141 AC: 135 AN: 95547 Hom.: 0 AF XY: 0.000992 AC XY: 19 AN XY: 19153

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.000632

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000445

GnomAD4 exome AF: 0.000316 AC: 303 AN: 957676 Hom.: 1 Cov.: 22 AF XY: 0.000265 AC XY: 70 AN XY: 264086

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000529

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000265

Gnomad4 OTH exome AF: 0.000847

GnomAD4 genome AF: 0.00332 AC: 316 AN: 95136 Hom.: 4 Cov.: 17 AF XY: 0.00182 AC XY: 37 AN XY: 20360

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.000552

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000429

Gnomad4 OTH AF: 0.00158

Alfa AF: 0.00209 Hom.: 7

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	-0.53
Cadd	Benign	12
Dann	Benign	0.85
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: rs372057894; hg19: chrX-53222063;