11-61392630-G-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001173990.3(TMEM216):c.-2G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,535,262 control chromosomes in the GnomAD database, including 2,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.074 ( 1429 hom., cov: 32)
Exomes 𝑓: 0.0074 ( 1182 hom. )
Consequence
TMEM216
NM_001173990.3 5_prime_UTR
NM_001173990.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.83
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 11-61392630-G-T is Benign according to our data. Variant chr11-61392630-G-T is described in ClinVar as [Benign]. Clinvar id is 193188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM216 | NM_001173990.3 | c.-2G>T | 5_prime_UTR_variant | 1/5 | ENST00000515837.7 | ||
TMEM216 | NM_001173991.3 | c.-2G>T | 5_prime_UTR_variant | 1/5 | |||
TMEM216 | NM_001330285.2 | c.-199G>T | 5_prime_UTR_variant | 1/5 | |||
TMEM216 | NM_016499.6 | c.-199G>T | 5_prime_UTR_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM216 | ENST00000515837.7 | c.-2G>T | 5_prime_UTR_variant | 1/5 | 2 | NM_001173990.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0738 AC: 11223AN: 152108Hom.: 1415 Cov.: 32
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GnomAD3 exomes AF: 0.0157 AC: 2117AN: 134498Hom.: 248 AF XY: 0.0118 AC XY: 863AN XY: 73216
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GnomAD4 exome AF: 0.00739 AC: 10223AN: 1383034Hom.: 1182 Cov.: 32 AF XY: 0.00637 AC XY: 4350AN XY: 682482
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GnomAD4 genome AF: 0.0741 AC: 11274AN: 152228Hom.: 1429 Cov.: 32 AF XY: 0.0719 AC XY: 5350AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 26, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Joubert syndrome 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Meckel syndrome, type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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