rs755212754
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_006172.4(NPPA):c.252C>T(p.Thr84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,613,316 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
NPPA
NM_006172.4 synonymous
NM_006172.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.73
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 Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 1-11847311-G-A is Benign according to our data. Variant chr1-11847311-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 240292.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.73 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPPA | NM_006172.4 | c.252C>T | p.Thr84= | synonymous_variant | 2/3 | ENST00000376480.7 | |
NPPA-AS1 | NR_037806.1 | n.1480-123G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPPA | ENST00000376480.7 | c.252C>T | p.Thr84= | synonymous_variant | 2/3 | 1 | NM_006172.4 | P1 | |
CLCN6 | ENST00000446542.5 | n.782-123G>A | intron_variant, non_coding_transcript_variant | 1 | |||||
NPPA | ENST00000376476.1 | c.102C>T | p.Thr34= | synonymous_variant | 2/3 | 3 | |||
CLCN6 | ENST00000400892.3 | c.*1962-266G>A | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248728Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135104
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GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461140Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 726804
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74328
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrial fibrillation, familial, 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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