Variant chrX-53192587-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004187.5(KDM5C):c.*380G>A variant causes a 3 prime UTR 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 (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., 61 hem., cov: 20)

Exomes 𝑓: 0.0021 ( 2 hom. 241 hem. )

Consequence

KDM5C
NM_004187.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.652

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-53192587-C-T is Benign according to our data. Variant chrX-53192587-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219148.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00144 (157/109065) while in subpopulation NFE AF= 0.0013 (68/52261). AF 95% confidence interval is 0.00105. There are 1 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 61 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM5C	NM_004187.5 linkuse as main transcript	c.*380G>A		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.*380G>A		3_prime_UTR_variant	26/26	1	NM_004187.5	ENSP00000364550.4		P41229-1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

157

AN:

109011

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

AN XY:

31337

show subpopulations

Gnomad AFR

AF:

0.000134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000970

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00130

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00207

AC:

868

AN:

419740

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

241

AN XY:

117394

show subpopulations

Gnomad4 AFR exome

AF:

0.0000800

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.000755

GnomAD4 genome

AF:

0.00144

AC:

157

AN:

109065

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

AN XY:

31401

show subpopulations

Gnomad4 AFR

AF:

0.000134

Gnomad4 AMR

AF:

0.0000969

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.00130

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.000574

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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