rs73694953
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_153704.6(TMEM67):c.1518+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,555,762 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 87 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 65 hom. )
Consequence
TMEM67
NM_153704.6 intron
NM_153704.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.230
Genes affected
TMEM67 (HGNC:28396): (transmembrane protein 67) The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Meckel syndrome type 3 (MKS3) and Joubert syndrome type 6 (JBTS6). [provided by RefSeq, Nov 2008]
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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=-0.63).
BP6
?
Variant 8-93787967-T-C is Benign according to our data. Variant chr8-93787967-T-C is described in ClinVar as [Benign]. Clinvar id is 262742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM67 | NM_153704.6 | c.1518+18T>C | intron_variant | ENST00000453321.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM67 | ENST00000453321.8 | c.1518+18T>C | intron_variant | 1 | NM_153704.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0182 AC: 2768AN: 152100Hom.: 87 Cov.: 32
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GnomAD3 exomes AF: 0.00476 AC: 1195AN: 251258Hom.: 30 AF XY: 0.00368 AC XY: 500AN XY: 135802
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GnomAD4 exome AF: 0.00184 AC: 2578AN: 1403544Hom.: 65 Cov.: 25 AF XY: 0.00157 AC XY: 1101AN XY: 701940
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GnomAD4 genome ? AF: 0.0183 AC: 2784AN: 152218Hom.: 87 Cov.: 32 AF XY: 0.0177 AC XY: 1321AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at