rs139569882

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004187.5(KDM5C):c.4637G>A(p.Arg1546Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000421 in 1,185,458 control chromosomes in the GnomAD database, including 3 homozygotes. There are 180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., 16 hem., cov: 20)

Exomes 𝑓: 0.00041 ( 3 hom. 164 hem. )

Consequence

KDM5C
NM_004187.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.136

Publications

4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069860816).

BP6

Variant X-53193013-C-T is Benign according to our data. Variant chrX-53193013-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 94879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 16 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004187.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM5C	NM_004187.5	MANE Select	c.4637G>A	p.Arg1546Gln	missense	Exon 26 of 26	NP_004178.2	P41229-1
KDM5C	NM_001282622.3		c.4634G>A	p.Arg1545Gln	missense	Exon 26 of 26	NP_001269551.1	P41229-5
KDM5C	NM_001353978.3		c.4628G>A	p.Arg1543Gln	missense	Exon 26 of 26	NP_001340907.1	P41229-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM5C	ENST00000375401.8	TSL:1 MANE Select	c.4637G>A	p.Arg1546Gln	missense	Exon 26 of 26	ENSP00000364550.4	P41229-1
KDM5C	ENST00000404049.7	TSL:1	c.4634G>A	p.Arg1545Gln	missense	Exon 26 of 26	ENSP00000385394.3	P41229-5
KDM5C	ENST00000935430.1		c.4739G>A	p.Arg1580Gln	missense	Exon 27 of 27	ENSP00000605489.1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

108997

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.000678

GnomAD2 exomes

AF:

0.000626

AC:

100

AN:

159704

AF XY:

0.000528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000714

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000410

AC:

441

AN:

1076461

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

164

AN XY:

349197

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26071

American (AMR)

AF:

0.00

AC:

AN:

33797

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

317

AN:

17629

East Asian (EAS)

AF:

0.00

AC:

AN:

29989

South Asian (SAS)

AF:

0.0000399

AC:

AN:

50107

European-Finnish (FIN)

AF:

0.0000757

AC:

AN:

39614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3949

European-Non Finnish (NFE)

AF:

0.0000867

AC:

AN:

830221

Other (OTH)

AF:

0.00104

AC:

AN:

45084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.000532

AC:

AN:

108997

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

31337

show subpopulations

African (AFR)

AF:

0.0000335

AC:

AN:

29845

American (AMR)

AF:

0.00

AC:

AN:

10404

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

2603

East Asian (EAS)

AF:

0.00

AC:

AN:

3353

South Asian (SAS)

AF:

0.00

AC:

AN:

2486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

229

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

52177

Other (OTH)

AF:

0.000678

AC:

AN:

1476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.000856

Hom.:

Bravo

AF:

0.000495

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000670

AC:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.20

PhyloP100

-0.14

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.010

REVEL

Benign

0.18

Sift

Benign

0.36

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.12

MVP

0.29

MPC

0.63

ClinPred

0.027

GERP RS

0.044

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.26

Mutation Taster

=100/0

polymorphism

(source)

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

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