X-53192861-A-AC

Variant summary

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

The NM_004187.5(KDM5C):c.*105_*106insG 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 0.77 (19525 hom., 6497 hem., cov: 0)
  • Exomes 𝑓: 0.84 (103045 hom. 76542 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM5C NM_004187.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.380

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-53192861-A-AC is Benign according to our data. Variant chrX-53192861-A-AC is described in ClinVar as [Benign]. Clinvar id is 1236561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 19516 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM5C	NM_004187.5	c.*105_*106insG		3_prime_UTR_variant	26/26	ENST00000375401.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM5C	ENST00000375401.8	c.*105_*106insG		3_prime_UTR_variant	26/26	1	NM_004187.5	P5

Frequencies

GnomAD3 genomes AF: 0.774 AC: 52588 AN: 67909 Hom.: 19516 Cov.: 0 AF XY: 0.665 AC XY: 6494 AN XY: 9763

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.942

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.786

GnomAD3 exomes AF: 0.885 AC: 62533 AN: 70635 Hom.: 23130 AF XY: 0.880 AC XY: 11575 AN XY: 13157

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.864

Gnomad ASJ exome AF: 0.931

Gnomad EAS exome AF: 0.807

Gnomad SAS exome AF: 0.949

Gnomad FIN exome AF: 0.938

Gnomad NFE exome AF: 0.945

Gnomad OTH exome AF: 0.911

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.839 AC: 332224 AN: 396171 Hom.: 103045 Cov.: 14 AF XY: 0.918 AC XY: 76542 AN XY: 83373

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.942

Gnomad4 FIN exome AF: 0.924

Gnomad4 NFE exome AF: 0.849

Gnomad4 OTH exome AF: 0.810

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.774 AC: 52611 AN: 67958 Hom.: 19525 Cov.: 0 AF XY: 0.664 AC XY: 6497 AN XY: 9782

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.911

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.786

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

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs146836963; hg19: chrX-53222043;