rs199422237

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004187.5(KDM5C):​c.1353C>T​(p.Ser451Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,209,973 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

KDM5C
NM_004187.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Publications

10 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, G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • X-linked syndromic intellectual disability
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant X-53211545-G-A is Benign according to our data. Variant chrX-53211545-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2660596.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.26 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM5CNM_004187.5 linkc.1353C>T p.Ser451Ser synonymous_variant Exon 10 of 26 ENST00000375401.8 NP_004178.2 P41229-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM5CENST00000375401.8 linkc.1353C>T p.Ser451Ser synonymous_variant Exon 10 of 26 1 NM_004187.5 ENSP00000364550.4 P41229-1

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112113
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000946
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000368
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000164
AC:
3
AN:
183307
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000730
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000273
AC:
3
AN:
1097807
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
363167
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26394
American (AMR)
AF:
0.0000568
AC:
2
AN:
35204
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19381
East Asian (EAS)
AF:
0.0000331
AC:
1
AN:
30205
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54120
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40528
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4136
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
841753
Other (OTH)
AF:
0.00
AC:
0
AN:
46086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000178
AC:
2
AN:
112166
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34344
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
30904
American (AMR)
AF:
0.0000945
AC:
1
AN:
10580
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2654
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3584
South Asian (SAS)
AF:
0.000369
AC:
1
AN:
2711
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6084
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
216
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
53218
Other (OTH)
AF:
0.00
AC:
0
AN:
1527
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

KDM5C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.46
DANN
Benign
0.85
PhyloP100
-1.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Mutation Taster
=90/10
polymorphism

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

Other links and lift over

dbSNP: rs199422237; hg19: chrX-53240727; API