X-53192858-GCCACCCCCCTACCCGC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004187.5(KDM5C):c.*93_*108del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (17 hom., 363 hem., cov: 0)
  • Exomes 𝑓: 0.021 (398 hom. 4898 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23

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.

• BP6: Variant X-53192858-GCCACCCCCCTACCCGC-G is Benign according to our data. Variant chrX-53192858-GCCACCCCCCTACCCGC-G is described in ClinVar as [Benign]. Clinvar id is 1183224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.*93_*108del		3_prime_UTR_variant	26/26	ENST00000375401.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5C	ENST00000375401.8	c.*93_*108del		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1159 AN: 24009 Hom.: 17 Cov.: 0 AF XY: 0.0822 AC XY: 361 AN XY: 4393 FAILED QC

Gnomad AFR AF: 0.00371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0895

Gnomad EAS AF: 0.00272

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.0649

GnomAD3 exomes AF: 0.147 AC: 1808 AN: 12274 Hom.: 21 AF XY: 0.265 AC XY: 543 AN XY: 2046

Gnomad AFR exome AF: 0.00387

Gnomad AMR exome AF: 0.0513

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.00119

Gnomad SAS exome AF: 0.416

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.176

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0214 AC: 15082 AN: 703424 Hom.: 398 AF XY: 0.0318 AC XY: 4898 AN XY: 154146

Gnomad4 AFR exome AF: 0.00231

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.0159

Gnomad4 EAS exome AF: 0.0000499

Gnomad4 SAS exome AF: 0.0275

Gnomad4 FIN exome AF: 0.0518

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0205

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0482 AC: 1159 AN: 24049 Hom.: 17 Cov.: 0 AF XY: 0.0821 AC XY: 363 AN XY: 4421

Gnomad4 AFR AF: 0.00364

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.0895

Gnomad4 EAS AF: 0.00274

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0284 Hom.: 118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200899285; hg19: chrX-53222040;