chr11-61392657-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001173990.3(TMEM216):c.26C>T(p.Ala9Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,534,792 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A9A) has been classified as Likely benign.
Frequency
Consequence
NM_001173990.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM216 | NM_001173990.3 | c.26C>T | p.Ala9Val | missense_variant | 1/5 | ENST00000515837.7 | |
TMEM216 | NM_001173991.3 | c.26C>T | p.Ala9Val | missense_variant | 1/5 | ||
TMEM216 | NM_001330285.2 | c.-172C>T | 5_prime_UTR_variant | 1/5 | |||
TMEM216 | NM_016499.6 | c.-172C>T | 5_prime_UTR_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM216 | ENST00000515837.7 | c.26C>T | p.Ala9Val | missense_variant | 1/5 | 2 | NM_001173990.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000743 AC: 1AN: 134634Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 73314
GnomAD4 exome AF: 0.0000181 AC: 25AN: 1382658Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 15AN XY: 682314
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2023 | The c.26C>T (p.A9V) alteration is located in exon 1 (coding exon 1) of the TMEM216 gene. This alteration results from a C to T substitution at nucleotide position 26, causing the alanine (A) at amino acid position 9 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Joubert syndrome 2 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 14, 2020 | - - |
Familial aplasia of the vermis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 9 of the TMEM216 protein (p.Ala9Val). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TMEM216-related conditions. ClinVar contains an entry for this variant (Variation ID: 991117). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at