rs386834205
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_153704.6(TMEM67):c.675G>A(p.Trp225Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_153704.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM67 | NM_153704.6 | c.675G>A | p.Trp225Ter | stop_gained | 7/28 | ENST00000453321.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM67 | ENST00000453321.8 | c.675G>A | p.Trp225Ter | stop_gained | 7/28 | 1 | NM_153704.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250850Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135522
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460536Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726510
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 08, 2023 | ClinVar contains an entry for this variant (Variation ID: 56787). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with TMEM67-related conditions (PMID: 19058225). This variant is present in population databases (rs386834205, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Trp225*) in the TMEM67 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TMEM67 are known to be pathogenic (PMID: 20232449, 23559409). - |
Meckel syndrome, type 3 Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Joubert syndrome 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at