chr8-93786286-GA-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_153704.6(TMEM67):βc.1353delβ(p.Glu452LysfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. R451R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_153704.6 frameshift
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.1353del | p.Glu452LysfsTer4 | frameshift_variant | 13/28 | ENST00000453321.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM67 | ENST00000453321.8 | c.1353del | p.Glu452LysfsTer4 | frameshift_variant | 13/28 | 1 | NM_153704.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251376Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135866
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727156
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Meckel syndrome, type 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province | Nov 18, 2021 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | This sequence change creates a premature translational stop signal (p.Glu452Lysfs*4) 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). This variant is present in population databases (rs749435317, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with nephronophthisis (PMID: 27491411). ClinVar contains an entry for this variant (Variation ID: 225493). For these reasons, this variant has been classified as Pathogenic. - |
Bardet-Biedl syndrome;C1853153:Joubert syndrome 6;C5435651:COACH syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at