rs727504847
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020297.4(ABCC9):c.3315+4A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00000137 in 1,460,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ABCC9
NM_020297.4 splice_donor_region, intron
NM_020297.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.8618
2
Clinical Significance
Conservation
PhyloP100: 4.16
Genes affected
ABCC9 (HGNC:60): (ATP binding cassette subfamily C member 9) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel-modulating subunit of the extra-pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated with cardiomyopathy dilated type 1O. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.3315+4A>G | splice_donor_region_variant, intron_variant | ENST00000261200.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.3315+4A>G | splice_donor_region_variant, intron_variant | 5 | NM_020297.4 | P4 | |||
ENST00000539874.1 | n.331+13285T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460050Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726446
GnomAD4 exome
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2
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1460050
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30
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1
AN XY:
726446
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 02, 2014 | The 3315+4A>G variant in ABCC9 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. This variant is located in th e 5' splice region. Computational tools raise the possibility that a new splice site might be created, though this information is not predictive enough to deter mine pathogenicity. Additional information is needed to fully assess the clinica l significance of this variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at