X-53192868-T-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.*99A>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 0.059 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.030 (2 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249

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=-0.89).
• BP6: Variant X-53192868-T-C is Benign according to our data. Variant chrX-53192868-T-C is described in ClinVar as [Benign]. Clinvar id is 1296681.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.*99A>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.*99A>G		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1302 AN: 22123 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3249 FAILED QC

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.00380 AC: 195 AN: 51256 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9684

Gnomad AFR exome AF: 0.00351

Gnomad AMR exome AF: 0.00657

Gnomad ASJ exome AF: 0.00285

Gnomad EAS exome AF: 0.00781

Gnomad SAS exome AF: 0.00317

Gnomad FIN exome AF: 0.000113

Gnomad NFE exome AF: 0.00421

Gnomad OTH exome AF: 0.00565

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0300 AC: 3844 AN: 128079 Hom.: 2 Cov.: 0 AF XY: 0.000116 AC XY: 3 AN XY: 25889

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.0281

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.0287

Gnomad4 FIN exome AF: 0.0169

Gnomad4 NFE exome AF: 0.0339

Gnomad4 OTH exome AF: 0.0348

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0588 AC: 1302 AN: 22155 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3259

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.0417

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.0483

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.0673

Alfa AF: 0.00222 Hom.: 0

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 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.66
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: rs781849827; hg19: chrX-53222050; COSMIC: COSV104428166; COSMIC: COSV104428166;