rs1423014570
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_001379110.1(SLC9A6):c.516C>T(p.Phe172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000864 in 1,156,956 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Genomes: 𝑓 0.000019 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000076 ( 0 hom. 1 hem. )
Consequence
SLC9A6
NM_001379110.1 synonymous
NM_001379110.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.104
Genes affected
SLC9A6 (HGNC:11079): (solute carrier family 9 member A6) This gene encodes a sodium-hydrogen exchanger that is amember of the solute carrier family 9. The encoded protein localizes to early and recycling endosomes and may be involved in regulating endosomal pH and volume. Defects in this gene are associated with X-linked syndromic cognitive disability, Christianson type. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant X-135998550-C-T is Benign according to our data. Variant chrX-135998550-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 469637.Status of the report is reviewed_by_expert_panel, 3 stars.
BP7
?
Synonymous conserved (PhyloP=0.104 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC9A6 | NM_001379110.1 | c.516C>T | p.Phe172= | synonymous_variant | 5/18 | ENST00000630721.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC9A6 | ENST00000630721.3 | c.516C>T | p.Phe172= | synonymous_variant | 5/18 | 4 | NM_001379110.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000186 AC: 2AN: 107808Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 31028
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GnomAD4 exome AF: 0.00000763 AC: 8AN: 1049148Hom.: 0 Cov.: 26 AF XY: 0.00000310 AC XY: 1AN XY: 322382
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Christianson syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2021 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Oct 13, 2023 | The p.Phe192= variant in SLC9A6 (NM_006359.2) is observed in the hemizygous state in at least 3 unaffected individuals (internal database - GeneDx) (BS2). The p.Phe172= variant in SLC9A6 is absent from gnomAD (PM2_Supporting). The silent p.Phe172= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). In the absence of other pathogenic evidence beyond PM2_Supporting, and because this variant has been observed in 3 unaffected hemizygous individuals, the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel has agreed to overrule the PM2_Supporting criterion and classified the p.Phe192= variant in SLC9A6 as Likely Benign (BS2, BP4, BP7). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at