X-53192924-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004187.5(KDM5C):​c.*43G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 950,652 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., 0 hem., cov: 16)
Exomes 𝑓: 0.000028 ( 0 hom. 4 hem. )

Consequence

KDM5C
NM_004187.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.39

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: 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: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant X-53192924-C-T is Benign according to our data. Variant chrX-53192924-C-T is described in ClinVar as [Benign]. Clinvar id is 1258823.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000278 (24/863647) while in subpopulation AMR AF = 0.00116 (21/18136). AF 95% confidence interval is 0.000776. There are 0 homozygotes in GnomAdExome4. There are 4 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
BS2
High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM5CNM_004187.5 linkc.*43G>A 3_prime_UTR_variant Exon 26 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.*43G>A 3_prime_UTR_variant Exon 26 of 26 1 NM_004187.5 ENSP00000364550.4 P41229-1

Frequencies

GnomAD3 genomes
AF:
0.0000115
AC:
1
AN:
87005
Hom.:
0
Cov.:
16
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000150
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000158
AC:
20
AN:
126670
AF XY:
0.0000977
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00117
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:
0.000351
GnomAD4 exome
AF:
0.0000278
AC:
24
AN:
863647
Hom.:
0
Cov.:
30
AF XY:
0.0000148
AC XY:
4
AN XY:
270279
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
19537
American (AMR)
AF:
0.00116
AC:
21
AN:
18136
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
9221
East Asian (EAS)
AF:
0.00
AC:
0
AN:
14855
South Asian (SAS)
AF:
0.0000238
AC:
1
AN:
42037
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
24388
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2889
European-Non Finnish (NFE)
AF:
0.00000143
AC:
1
AN:
700697
Other (OTH)
AF:
0.0000314
AC:
1
AN:
31887
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
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:
0.0000115
AC:
1
AN:
87005
Hom.:
0
Cov.:
16
AF XY:
0.00
AC XY:
0
AN XY:
18427
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24176
American (AMR)
AF:
0.000150
AC:
1
AN:
6687
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2351
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2208
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1184
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
2996
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
155
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
45542
Other (OTH)
AF:
0.00
AC:
0
AN:
1166
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.0000980
Hom.:
0

ClinVar

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

Submissions by phenotype

not provided Benign:1
Apr 09, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
15
DANN
Benign
0.90
PhyloP100
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=100/0
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: rs781971436; hg19: chrX-53222106; API