X-53192869-A-C

Position:

• chrX-53192869-A-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.*98T>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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.0095 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.135

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]

KDM5C (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-53192869-A-C is Benign according to our data. Variant chrX-53192869-A-C is described in ClinVar as [Benign]. Clinvar id is 1260604.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM5C	NM_004187.5	c.*98T>G		3_prime_UTR_variant	26/26	ENST00000375401.8	NP_004178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000375401	c.*98T>G		3_prime_UTR_variant	26/26	1	NM_004187.5	ENSP00000364550.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 180 AN: 27056 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4906 FAILED QC

Gnomad AFR AF: 0.00342

Gnomad AMI AF: 0.0280

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00985

Gnomad EAS AF: 0.00165

Gnomad SAS AF: 0.00360

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00844

Gnomad OTH AF: 0.00809

GnomAD3 exomes AF: 0.000526 AC: 33 AN: 62692 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000201

Gnomad SAS exome AF: 0.000983

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00954 AC: 1414 AN: 148295 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 33115

Gnomad4 AFR exome AF: 0.00403

Gnomad4 AMR exome AF: 0.00690

Gnomad4 ASJ exome AF: 0.00548

Gnomad4 EAS exome AF: 0.00344

Gnomad4 SAS exome AF: 0.00472

Gnomad4 FIN exome AF: 0.00335

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.00933

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00665 AC: 180 AN: 27088 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4912

Gnomad4 AFR AF: 0.00342

Gnomad4 AMR AF: 0.00743

Gnomad4 ASJ AF: 0.00985

Gnomad4 EAS AF: 0.00165

Gnomad4 SAS AF: 0.00357

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.00843

Gnomad4 OTH AF: 0.00789

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

Mar 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.42
DANN	Benign	0.69

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: rs1569255847; hg19: chrX-53222051;