12-295567-C-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001042603.3(KDM5A):c.4455+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,612,628 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 1 hom. )
Consequence
KDM5A
NM_001042603.3 splice_donor_region, intron
NM_001042603.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00004841
2
Clinical Significance
Conservation
PhyloP100: 0.274
Genes affected
KDM5A (HGNC:9886): (lysine demethylase 5A) This gene encodes a member of the Jumonji, AT-rich interactive domain 1 (JARID1) histone demethylase protein family. The encoded protein plays a role in gene regulation through the histone code by specifically demethylating lysine 4 of histone H3. The encoded protein interacts with many other proteins, including retinoblastoma protein, and is implicated in the transcriptional regulation of Hox genes and cytokines. This gene may play a role in tumor progression. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 12-295567-C-A is Benign according to our data. Variant chr12-295567-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3046862.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM5A | NM_001042603.3 | c.4455+6G>T | splice_donor_region_variant, intron_variant | ENST00000399788.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM5A | ENST00000399788.7 | c.4455+6G>T | splice_donor_region_variant, intron_variant | 1 | NM_001042603.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000237 AC: 59AN: 248970Hom.: 0 AF XY: 0.000244 AC XY: 33AN XY: 135082
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GnomAD4 exome AF: 0.0000466 AC: 68AN: 1460356Hom.: 1 Cov.: 30 AF XY: 0.0000523 AC XY: 38AN XY: 726652
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KDM5A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 21, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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