rs34989098
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_173630.4(RTTN):c.6445G>A(p.Ala2149Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 1,613,800 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_173630.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTTN | NM_173630.4 | c.6445G>A | p.Ala2149Thr | missense_variant | 47/49 | ENST00000640769.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTTN | ENST00000640769.2 | c.6445G>A | p.Ala2149Thr | missense_variant | 47/49 | 2 | NM_173630.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00608 AC: 926AN: 152218Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.00577 AC: 1438AN: 249042Hom.: 9 AF XY: 0.00604 AC XY: 816AN XY: 135086
GnomAD4 exome AF: 0.00621 AC: 9077AN: 1461464Hom.: 63 Cov.: 29 AF XY: 0.00631 AC XY: 4587AN XY: 727056
GnomAD4 genome AF: 0.00609 AC: 927AN: 152336Hom.: 5 Cov.: 32 AF XY: 0.00589 AC XY: 439AN XY: 74506
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 20, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | RTTN: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Oct 07, 2015 | - - |
Microcephalic primordial dwarfism due to RTTN deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Possible pathogenicity based on finding it once in our laboratory in trans with another missense variant in a 3-year-old female with microcephaly, craniosynostosis, dysmorphisms, fused labia, absence seizures, failure to thrive. However, allele frequency is high, and homozygotes have been found in controls. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 05, 2015 | - - |
RTTN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 12, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at