rs5569
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001172501.3(SLC6A2):c.1287G>A(p.Thr429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,613,516 control chromosomes in the GnomAD database, including 88,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.27 ( 6254 hom., cov: 31)
Exomes 𝑓: 0.33 ( 81961 hom. )
Consequence
SLC6A2
NM_001172501.3 synonymous
NM_001172501.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.10
Genes affected
SLC6A2 (HGNC:11048): (solute carrier family 6 member 2) This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 16-55697923-G-A is Benign according to our data. Variant chr16-55697923-G-A is described in ClinVar as [Benign]. Clinvar id is 1283289.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.1 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A2 | NM_001172501.3 | c.1287G>A | p.Thr429= | synonymous_variant | 10/15 | ENST00000568943.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A2 | ENST00000568943.6 | c.1287G>A | p.Thr429= | synonymous_variant | 10/15 | 1 | NM_001172501.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.267 AC: 40573AN: 151886Hom.: 6249 Cov.: 31
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GnomAD3 exomes AF: 0.313 AC: 78531AN: 251250Hom.: 13223 AF XY: 0.308 AC XY: 41781AN XY: 135800
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GnomAD4 exome AF: 0.329 AC: 480647AN: 1461512Hom.: 81961 Cov.: 40 AF XY: 0.325 AC XY: 236147AN XY: 727072
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GnomAD4 genome ? AF: 0.267 AC: 40580AN: 152004Hom.: 6254 Cov.: 31 AF XY: 0.269 AC XY: 19969AN XY: 74300
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 28, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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