1-11847284-ATC-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_006172.4(NPPA):βc.277_278delβ(p.Asp93TrpfsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000868 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 32)
Exomes π: 0.0000082 ( 0 hom. )
Consequence
NPPA
NM_006172.4 frameshift
NM_006172.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.78
Genes affected
NPPA (HGNC:7939): (natriuretic peptide A) The protein encoded by this gene belongs to the natriuretic peptide family. Natriuretic peptides are implicated in the control of extracellular fluid volume and electrolyte homeostasis. This protein is synthesized as a large precursor (containing a signal peptide), which is processed to release a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. Mutations in this gene have been associated with atrial fibrillation familial type 6. This gene is located adjacent to another member of the natriuretic family of peptides on chromosome 1. [provided by RefSeq, Oct 2015]
CLCN6 (HGNC:2024): (chloride voltage-gated channel 6) This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NPPA | NM_006172.4 | c.277_278del | p.Asp93TrpfsTer13 | frameshift_variant | 2/3 | ENST00000376480.7 | NP_006163.1 | |
| NPPA-AS1 | NR_037806.1 | n.1480-144_1480-143del | intron_variant, non_coding_transcript_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NPPA | ENST00000376480.7 | c.277_278del | p.Asp93TrpfsTer13 | frameshift_variant | 2/3 | 1 | NM_006172.4 | ENSP00000365663 | P1 | |
| CLCN6 | ENST00000446542.5 | n.782-144_782-143del | intron_variant, non_coding_transcript_variant | 1 | ||||||
| NPPA | ENST00000376476.1 | c.127_128del | p.Asp43TrpfsTer13 | frameshift_variant | 2/3 | 3 | ENSP00000365659 | |||
| CLCN6 | ENST00000400892.3 | c.*1962-287_*1962-286del | intron_variant, NMD_transcript_variant | 3 | ENSP00000496938 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249208Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135356
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461386Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 726942
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GnomAD4 genome 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrial fibrillation, familial, 6 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 12, 2022 | This sequence change creates a premature translational stop signal (p.Asp93Trpfs*13) in the NPPA gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NPPA cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 537322). This variant has not been reported in the literature in individuals affected with NPPA-related conditions. This variant is present in population databases (rs774165756, gnomAD 0.02%). - |
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at