Variant X-53192843-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001146702.2(KDM5C):c.4047-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.018 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

KDM5C
NM_001146702.2 splice_region, intron

Scores

Splicing: ADA: 0.000009886

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.911

Variant links:

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 links:

KDM5C (HGNC:):

KDM5C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-53192843-C-G is Benign according to our data. Variant chrX-53192843-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2283519.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chrX-53192843-C-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM5C	NM_004187.5 linkuse as main transcript	c.*124G>C		3_prime_UTR_variant	26/26	ENST00000375401.8	NP_004178.2	P41229-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000375401 linkuse as main transcript	c.*124G>C		3_prime_UTR_variant	26/26	1	NM_004187.5	ENSP00000364550.4		P41229-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

88594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

18550

FAILED QC

Gnomad AFR

AF:

0.0000393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000434

Gnomad EAS

AF:

0.000484

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0177

AC:

8192

AN:

463493

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

120975

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00859

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.00391

Gnomad4 FIN exome

AF:

0.00249

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000677

AC:

AN:

88669

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

18593

show subpopulations

Gnomad4 AFR

AF:

0.0000393

Gnomad4 AMR

AF:

0.000130

Gnomad4 ASJ

AF:

0.000434

Gnomad4 EAS

AF:

0.000485

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2022

The c.4047-6G>C intronic alteration consists of a G to C substitution 6 nucleotides before coding exon 24 in the KDM5C gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

KDM5C: BP4 -

KDM5C-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000099

dbscSNV1_RF

Benign

0.0

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over