rs11230683
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001173990.3(TMEM216):c.253C>A(p.Arg85Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000649 in 1,613,490 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 5 hom., cov: 31)
Exomes 𝑓: 0.00061 ( 22 hom. )
Consequence
TMEM216
NM_001173990.3 synonymous
NM_001173990.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.26
Genes affected
TMEM216 (HGNC:25018): (transmembrane protein 216) This locus encodes a transmembrane domain-containing protein. Mutations at this locus have been associated with Meckel-Gruber Syndrome Type 2, and Joubert Syndrome 2, also known as Cerebello-oculorenal Syndrome 2. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 11-61397797-C-A is Benign according to our data. Variant chr11-61397797-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 282947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61397797-C-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.26 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00104 (158/152324) while in subpopulation EAS AF= 0.0285 (148/5184). AF 95% confidence interval is 0.0248. There are 5 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM216 | NM_001173990.3 | c.253C>A | p.Arg85Arg | synonymous_variant | 4/5 | ENST00000515837.7 | NP_001167461.1 | |
TMEM216 | NM_001173991.3 | c.253C>A | p.Arg85Arg | synonymous_variant | 4/5 | NP_001167462.1 | ||
TMEM216 | NM_016499.6 | c.70C>A | p.Arg24Arg | synonymous_variant | 4/5 | NP_057583.2 | ||
TMEM216 | NM_001330285.2 | c.70C>A | p.Arg24Arg | synonymous_variant | 4/5 | NP_001317214.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM216 | ENST00000515837.7 | c.253C>A | p.Arg85Arg | synonymous_variant | 4/5 | 2 | NM_001173990.3 | ENSP00000440638.1 | ||
TMEM216 | ENST00000334888.10 | c.253C>A | p.Arg85Arg | synonymous_variant | 4/5 | 2 | ENSP00000334844.5 |
Frequencies
GnomAD3 genomes AF: 0.00104 AC: 158AN: 152206Hom.: 5 Cov.: 31
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GnomAD3 exomes AF: 0.00278 AC: 691AN: 248910Hom.: 17 AF XY: 0.00261 AC XY: 353AN XY: 134992
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GnomAD4 genome AF: 0.00104 AC: 158AN: 152324Hom.: 5 Cov.: 31 AF XY: 0.00118 AC XY: 88AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 05, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 04, 2015 | - - |
Meckel syndrome, type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Joubert syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
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