X-53192834-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004187.5(KDM5C):c.*133T>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 0.000064 (0 hom., 0 hem., cov: 18)
  • Exomes 𝑓: 0.0037 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.471

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-53192834-A-T is Benign according to our data. Variant chrX-53192834-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049335.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.*133T>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.*133T>A		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6 AN: 93712 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 22020 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000456

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000854

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00370 AC: 2094 AN: 565247 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 153853

Gnomad4 AFR exome AF: 0.00307

Gnomad4 AMR exome AF: 0.000309

Gnomad4 ASJ exome AF: 0.00243

Gnomad4 EAS exome AF: 0.00199

Gnomad4 SAS exome AF: 0.000891

Gnomad4 FIN exome AF: 0.0000793

Gnomad4 NFE exome AF: 0.00456

Gnomad4 OTH exome AF: 0.00305

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000640 AC: 6 AN: 93793 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 22081

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000115

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000457

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000854

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KDM5C-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 08, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.2
Dann	Benign	0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-53222016;