rs143955805

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004187.5(KDM5C):c.2823A>G(p.Ser941Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,207,911 control chromosomes in the GnomAD database, including 2 homozygotes. There are 477 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., 53 hem., cov: 25)

Exomes 𝑓: 0.0012 ( 1 hom. 424 hem. )

Consequence

KDM5C
NM_004187.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.00400

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-53196844-T-C is Benign according to our data. Variant chrX-53196844-T-C is described in ClinVar as [Benign]. Clinvar id is 211248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53196844-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00138 (157/113510) while in subpopulation AMR AF= 0.0034 (37/10880). AF 95% confidence interval is 0.00254. There are 1 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 53 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5C	NM_004187.5 link	c.2823A>G	p.Ser941Ser	synonymous_variant	Exon 19 of 26	ENST00000375401.8	NP_004178.2	P41229-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000375401.8 link	c.2823A>G	p.Ser941Ser	synonymous_variant	Exon 19 of 26	1	NM_004187.5	ENSP00000364550.4		P41229-1

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

157

AN:

113459

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

AN XY:

35593

show subpopulations

Gnomad AFR

AF:

0.000352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00639

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000702

Gnomad FIN

AF:

0.00251

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00133

Gnomad OTH

AF:

0.00195

GnomAD3 exomes

AF:

0.00131

AC:

224

AN:

171337

Hom.:

AF XY:

0.00145

AC XY:

AN XY:

57875

show subpopulations

Gnomad AFR exome

AF:

0.000163

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00482

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000335

Gnomad FIN exome

AF:

0.00300

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.00330

GnomAD4 exome

AF:

0.00119

AC:

1306

AN:

1094401

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

424

AN XY:

360161

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00638

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000355

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00138

AC:

157

AN:

113510

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

AN XY:

35654

show subpopulations

Gnomad4 AFR

AF:

0.000351

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00639

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000703

Gnomad4 FIN

AF:

0.00251

Gnomad4 NFE

AF:

0.00133

Gnomad4 OTH

AF:

0.00193

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00151

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 24, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 02, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spastic paraplegia

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KDM5C-related disorder

Benign:1

Apr 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

-0.80

CADD

Benign

9.6

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over