chr14-69952261-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001034852.3(SMOC1):c.223C>T(p.Arg75*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,066 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_001034852.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMOC1 | NM_001034852.3 | c.223C>T | p.Arg75* | stop_gained | Exon 2 of 12 | ENST00000361956.8 | NP_001030024.1 | |
SMOC1 | NM_001425244.1 | c.223C>T | p.Arg75* | stop_gained | Exon 2 of 12 | NP_001412173.1 | ||
SMOC1 | NM_001425245.1 | c.223C>T | p.Arg75* | stop_gained | Exon 2 of 12 | NP_001412174.1 | ||
SMOC1 | NM_022137.6 | c.223C>T | p.Arg75* | stop_gained | Exon 2 of 12 | NP_071420.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMOC1 | ENST00000361956.8 | c.223C>T | p.Arg75* | stop_gained | Exon 2 of 12 | 1 | NM_001034852.3 | ENSP00000355110.4 | ||
SMOC1 | ENST00000381280.4 | c.223C>T | p.Arg75* | stop_gained | Exon 2 of 12 | 1 | ENSP00000370680.4 | |||
SMOC1 | ENST00000553839.1 | n.125C>T | non_coding_transcript_exon_variant | Exon 1 of 4 | 5 | |||||
SMOC1 | ENST00000555917.1 | n.528C>T | non_coding_transcript_exon_variant | Exon 4 of 4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251332Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135820
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461872Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727242
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 21750680, 31067494) - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 12, 2024 | This sequence change creates a premature translational stop signal (p.Arg75*) in the SMOC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMOC1 are known to be pathogenic (PMID: 21194678). This variant is present in population databases (rs370866589, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with ophthalmo-acromelic syndrome (PMID: 21750680, 31067494). ClinVar contains an entry for this variant (Variation ID: 599220). For these reasons, this variant has been classified as Pathogenic. - |
Microphthalmia with limb anomalies Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Hacettepe Genetic Diseases Diagnosis Center, Hacettepe University Faculty of Medicine | Nov 23, 2017 | The p.Arg75Ter variant in SMOC1 has been observed for a 9-month-old Turkish female patient who was diagnosed with ophthalmo-acromelic syndrome. There was parental consanguinity and autosomal recessive inheritance pattern matching for this variant. In summary, the p.Arg75Ter variant meets our criteria to be classified as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at