Genetic Variant KDM5C:c.*124G>A (chrX-53192843-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001146702.2(KDM5C):c.4047-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., 2 hem., cov: 18)

Exomes 𝑓: 0.000055 ( 0 hom. 10 hem. )

Consequence

KDM5C
NM_001146702.2 splice_region, intron

Scores

Splicing: ADA: 0.000009886

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.911

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Claes-Jensen type
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

KDM5C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-53192843-C-T is Benign according to our data. Variant chrX-53192843-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1254243.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146702.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM5C	NM_004187.5	MANE Select	c.*124G>A	3_prime_UTR	Exon 26 of 26	NP_004178.2	P41229-1
KDM5C	NM_001282622.3		c.*124G>A	3_prime_UTR	Exon 26 of 26	NP_001269551.1	P41229-5
KDM5C	NM_001353978.3		c.*124G>A	3_prime_UTR	Exon 26 of 26	NP_001340907.1	P41229-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM5C	ENST00000375401.8	TSL:1 MANE Select	c.*124G>A	3_prime_UTR	Exon 26 of 26	ENSP00000364550.4	P41229-1
KDM5C	ENST00000404049.7	TSL:1	c.*124G>A	3_prime_UTR	Exon 26 of 26	ENSP00000385394.3	P41229-5
KDM5C	ENST00000935430.1		c.*124G>A	3_prime_UTR	Exon 27 of 27	ENSP00000605489.1

Frequencies

GnomAD3 genomes

AF:

0.0000339

AC:

AN:

88595

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00161

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000100

AC:

AN:

90021

AF XY:

0.0000506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000708

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000549

AC:

AN:

473169

Hom.:

Cov.:

AF XY:

0.0000786

AC XY:

AN XY:

127167

show subpopulations

African (AFR)

AF:

0.0000794

AC:

AN:

12588

American (AMR)

AF:

0.0000487

AC:

AN:

20543

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10525

East Asian (EAS)

AF:

0.00

AC:

AN:

15365

South Asian (SAS)

AF:

0.000340

AC:

AN:

35267

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24923

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1761

European-Non Finnish (NFE)

AF:

0.0000241

AC:

AN:

331541

Other (OTH)

AF:

0.000194

AC:

AN:

20656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000339

AC:

AN:

88595

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

18551

show subpopulations

African (AFR)

AF:

0.0000393

AC:

AN:

25422

American (AMR)

AF:

0.00

AC:

AN:

7646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2302

East Asian (EAS)

AF:

0.00

AC:

AN:

2065

South Asian (SAS)

AF:

0.00161

AC:

AN:

1241

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

146

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

45162

Other (OTH)

AF:

0.00

AC:

AN:

1210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.9

(source)

DANN

Benign

0.56

PhyloP100

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000099

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over