X-53192873-G-C

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.*94C>G 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 0.10 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.12 (0 hom. 1 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: 0.0280

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=-0.8).
• BP6: Variant X-53192873-G-C is Benign according to our data. Variant chrX-53192873-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1215665.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.*94C>G		3_prime_UTR_variant	26/26	ENST00000375401.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5C	ENST00000375401.8	c.*94C>G		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2031 AN: 19635 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2713 FAILED QC

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0933

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.126

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.119 AC: 17673 AN: 148476 Hom.: 0 Cov.: 5 AF XY: 0.0000363 AC XY: 1 AN XY: 27574

Gnomad4 AFR exome AF: 0.0710

Gnomad4 AMR exome AF: 0.0532

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.0655

Gnomad4 SAS exome AF: 0.0756

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.103 AC: 2030 AN: 19656 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2722

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.0766

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0703

Gnomad4 SAS AF: 0.0558

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.123

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

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.84
Dann	Benign	0.70

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: rs782275907; hg19: chrX-53222055;