rs386833830
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_001173990.3(TMEM216):c.230G>C(p.Gly77Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
TMEM216
NM_001173990.3 missense, splice_region
NM_001173990.3 missense, splice_region
Scores
7
11
1
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 6.44
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a chain Transmembrane protein 216 (size 144) in uniprot entity TM216_HUMAN there are 13 pathogenic changes around while only 5 benign (72%) in NM_001173990.3
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.
PP5
?
Variant 11-61397774-G-C is Pathogenic according to our data. Variant chr11-61397774-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 200.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-61397774-G-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM216 | NM_001173990.3 | c.230G>C | p.Gly77Ala | missense_variant, splice_region_variant | 4/5 | ENST00000515837.7 | |
TMEM216 | NM_001173991.3 | c.230G>C | p.Gly77Ala | missense_variant, splice_region_variant | 4/5 | ||
TMEM216 | NM_016499.6 | c.47G>C | p.Gly16Ala | missense_variant, splice_region_variant | 4/5 | ||
TMEM216 | NM_001330285.2 | c.47G>C | p.Gly16Ala | missense_variant, splice_region_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM216 | ENST00000515837.7 | c.230G>C | p.Gly77Ala | missense_variant, splice_region_variant | 4/5 | 2 | NM_001173990.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Meckel syndrome, type 2 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2010 | - - |
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
T;T;T
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -46
DS_AL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at