rs151178361
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4BP7BP5_StrongBS1BS2
This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Leu381= variant in SLC9A6 (NM_006359.2) is 0.024% in European (Non-Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The silent p.Leu381= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). The p.Leu381= variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2_strong). The p.Leu381= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong). In summary, the p.Leu381= variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BS1, BP4, BP7, BS2_strong, BP5_strong). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10524772/MONDO:0010278/033
Frequency
Consequence
NM_001379110.1 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC9A6 | NM_001379110.1 | c.1083G>A | p.Leu361= | splice_region_variant, synonymous_variant | 11/18 | ENST00000630721.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC9A6 | ENST00000630721.3 | c.1083G>A | p.Leu361= | splice_region_variant, synonymous_variant | 11/18 | 4 | NM_001379110.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000205 AC: 23AN: 111993Hom.: 0 Cov.: 22 AF XY: 0.000322 AC XY: 11AN XY: 34163
GnomAD3 exomes AF: 0.000148 AC: 27AN: 182825Hom.: 0 AF XY: 0.000163 AC XY: 11AN XY: 67329
GnomAD4 exome AF: 0.000198 AC: 199AN: 1004844Hom.: 0 Cov.: 21 AF XY: 0.000184 AC XY: 56AN XY: 304198
GnomAD4 genome ? AF: 0.000205 AC: 23AN: 111993Hom.: 0 Cov.: 22 AF XY: 0.000322 AC XY: 11AN XY: 34163
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | SLC9A6: BP4, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 14, 2016 | - - |
Christianson syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Feb 23, 2024 | The allele frequency of the p.Leu381= variant in SLC9A6 (NM_006359.2) is 0.024% in European (Non-Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The silent p.Leu381= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). The p.Leu381= variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2_strong). The p.Leu381= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong). In summary, the p.Leu381= variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BS1, BP4, BP7, BS2_strong, BP5_strong). - |
SLC9A6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 27, 2023 | 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). - |
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 18, 2013 | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at