chrX-53192835-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_004187.5(KDM5C):c.*132C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000605 in 1,091,199 control chromosomes in the GnomAD database, including 1 homozygotes. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., 8 hem., cov: 19)
Exomes 𝑓: 0.000029 ( 1 hom. 4 hem. )
Consequence
KDM5C
NM_004187.5 3_prime_UTR
NM_004187.5 3_prime_UTR
Scores
1
12
Splicing: ADA: 0.00006871
2
Clinical Significance
Conservation
PhyloP100: 0.885
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1330562).
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000375 (37/98685) while in subpopulation AMR AF= 0.00379 (34/8977). AF 95% confidence interval is 0.00279. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High Hemizygotes in GnomAd at 8 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5C | NM_004187.5 | c.*132C>G | 3_prime_UTR_variant | 26/26 | ENST00000375401.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5C | ENST00000375401.8 | c.*132C>G | 3_prime_UTR_variant | 26/26 | 1 | NM_004187.5 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000375 AC: 37AN: 98628Hom.: 0 Cov.: 19 AF XY: 0.000353 AC XY: 8AN XY: 22638
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GnomAD3 exomes AF: 0.0000493 AC: 5AN: 101407Hom.: 0 AF XY: 0.0000777 AC XY: 2AN XY: 25725
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GnomAD4 exome AF: 0.0000292 AC: 29AN: 992514Hom.: 1 Cov.: 21 AF XY: 0.0000134 AC XY: 4AN XY: 297710
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GnomAD4 genome ? AF: 0.000375 AC: 37AN: 98685Hom.: 0 Cov.: 19 AF XY: 0.000352 AC XY: 8AN XY: 22703
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Loss of loop (P = 0.0073);
MVP
ClinPred
T
GERP RS
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at