chrX-53201956-C-T

Position:

chrX-53201956-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_004187.5(KDM5C):c.1764G>A(p.Gln588Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00356 in 1,210,364 control chromosomes in the GnomAD database, including 10 homozygotes. There are 1,364 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., 84 hem., cov: 23)

Exomes 𝑓: 0.0036 ( 9 hom. 1280 hem. )

Consequence

KDM5C
NM_004187.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 4.17

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant X-53201956-C-T is Benign according to our data. Variant chrX-53201956-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 166871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53201956-C-T is described in Lovd as [Benign]. Variant chrX-53201956-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00287 (322/112344) while in subpopulation NFE AF= 0.0049 (261/53263). AF 95% confidence interval is 0.00441. There are 1 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 84 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM5C	NM_004187.5 linkuse as main transcript	c.1764G>A	p.Gln588Gln	synonymous_variant	13/26	ENST00000375401.8	NP_004178.2	P41229-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM5C	ENST00000375401.8 linkuse as main transcript	c.1764G>A	p.Gln588Gln	synonymous_variant	13/26	1	NM_004187.5	ENSP00000364550.4		P41229-1

Frequencies

GnomAD3 genomes

AF:

0.00287

AC:

322

AN:

112291

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

AN XY:

34433

show subpopulations

Gnomad AFR

AF:

0.000357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00245

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000727

Gnomad FIN

AF:

0.00180

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00490

Gnomad OTH

AF:

0.00399

GnomAD3 exomes

AF:

0.00266

AC:

489

AN:

183506

Hom.:

AF XY:

0.00290

AC XY:

197

AN XY:

67936

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00126

Gnomad FIN exome

AF:

0.00119

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00363

AC:

3989

AN:

1098020

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

1280

AN XY:

363378

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00431

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00287

AC:

322

AN:

112344

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

AN XY:

34496

show subpopulations

Gnomad4 AFR

AF:

0.000356

Gnomad4 AMR

AF:

0.00245

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000729

Gnomad4 FIN

AF:

0.00180

Gnomad4 NFE

AF:

0.00490

Gnomad4 OTH

AF:

0.00394

Alfa

AF:

0.00447

Hom.:

Bravo

AF:

0.00268

EpiCase

AF:

0.00311

EpiControl

AF:

0.00356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 24, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 04, 2016	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2019	This variant is associated with the following publications: (PMID: 19377476, 24583395) -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

KDM5C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 19, 2019

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

-0.38

CADD

Benign

6.4

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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