11-61364146-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_016464.5(TMEM138):c.-139-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 368,956 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.026 ( 198 hom., cov: 33)
Exomes 𝑓: 0.0036 ( 33 hom. )
Consequence
TMEM138
NM_016464.5 intron
NM_016464.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0280
Genes affected
TMEM138 (HGNC:26944): (transmembrane protein 138) This gene encodes a multi-pass transmembrane protein. Reduced expression of this gene in mouse fibroblasts causes short cilia and failure of ciliogenesis. Expression of this gene is tightly coordinated with expression of the neighboring gene TMEM216. Mutations in this gene are associated with the autosomal recessive neurodevelopmental disorder Joubert Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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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=-0.93).
BP6
Variant 11-61364146-A-G is Benign according to our data. Variant chr11-61364146-A-G is described in ClinVar as [Benign]. Clinvar id is 1253941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM138 | NM_016464.5 | c.-139-106A>G | intron_variant | ENST00000278826.11 | NP_057548.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM138 | ENST00000278826.11 | c.-139-106A>G | intron_variant | 1 | NM_016464.5 | ENSP00000278826.5 |
Frequencies
GnomAD3 genomes AF: 0.0262 AC: 3996AN: 152244Hom.: 196 Cov.: 33
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GnomAD4 exome AF: 0.00356 AC: 772AN: 216594Hom.: 33 Cov.: 3 AF XY: 0.00316 AC XY: 353AN XY: 111558
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GnomAD4 genome AF: 0.0262 AC: 3999AN: 152362Hom.: 198 Cov.: 33 AF XY: 0.0253 AC XY: 1887AN XY: 74516
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 30, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at