Variant X-53192606-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004187.5(KDM5C):c.*361C>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 0.012 ( 20 hom., 324 hem., cov: 20)

Exomes 𝑓: 0.0018 ( 11 hom. 223 hem. )

Consequence

KDM5C
NM_004187.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant X-53192606-G-T is Benign according to our data. Variant chrX-53192606-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1361/108945) while in subpopulation AFR AF= 0.0431 (1284/29793). AF 95% confidence interval is 0.0411. There are 20 homozygotes in gnomad4. There are 324 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM5C	NM_004187.5 linkuse as main transcript	c.*361C>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.*361C>A		3_prime_UTR_variant	26/26	1	NM_004187.5	ENSP00000364550.4		P41229-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1358

AN:

108896

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

319

AN XY:

31204

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000402

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000402

Gnomad OTH

AF:

0.00884

GnomAD4 exome

AF:

0.00176

AC:

909

AN:

515175

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

223

AN XY:

136819

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00227

Gnomad4 ASJ exome

AF:

0.000313

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000642

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.0125

AC:

1361

AN:

108945

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

324

AN XY:

31263

show subpopulations

Gnomad4 AFR

AF:

0.0431

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000402

Gnomad4 OTH

AF:

0.00873

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0148

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.6

DANN

Benign

0.82

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