Genetic Variant KDM5C:c.*133T>A (chrX-53192834-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001146702.2(KDM5C):c.4050T>A(p.Pro1350Pro) variant causes a synonymous 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 (no stars).

Frequency

Genomes: 𝑓 0.000064 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.0037 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

KDM5C
NM_001146702.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.471

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-53192834-A-T is Benign according to our data. Variant chrX-53192834-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049335.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.471 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5C	NM_004187.5 link	c.*133T>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000375401.8	NP_004178.2	P41229-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000375401 link	c.*133T>A		3_prime_UTR_variant	Exon 26 of 26	1	NM_004187.5	ENSP00000364550.4		P41229-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

93712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22020

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000115

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000456

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000854

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00370

AC:

2094

AN:

565247

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

153853

show subpopulations

Gnomad4 AFR exome

AF:

0.00307

Gnomad4 AMR exome

AF:

0.000309

Gnomad4 ASJ exome

AF:

0.00243

Gnomad4 EAS exome

AF:

0.00199

Gnomad4 SAS exome

AF:

0.000891

Gnomad4 FIN exome

AF:

0.0000793

Gnomad4 NFE exome

AF:

0.00456

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000640

AC:

AN:

93793

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22081

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000115

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000457

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000854

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KDM5C-related disorder

Benign:1

Feb 08, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.87

CADD

Benign

2.2

DANN

Benign

0.43

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

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