19-50476614-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_206538.4(EMC10):c.70C>T(p.Arg24*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 1,560,824 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 Likely pathogenic (★).
Frequency
Consequence
NM_206538.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMC10 | NM_206538.4 | c.70C>T | p.Arg24* | stop_gained | Exon 1 of 7 | ENST00000334976.11 | NP_996261.1 | |
GARIN5A | NM_001308429.2 | c.-226G>A | 5_prime_UTR_variant | Exon 1 of 5 | ENST00000600100.6 | NP_001295358.1 | ||
EMC10 | NM_175063.6 | c.70C>T | p.Arg24* | stop_gained | Exon 1 of 8 | NP_778233.4 | ||
GARIN5A | NM_138411.3 | c.-226G>A | 5_prime_UTR_variant | Exon 1 of 5 | NP_612420.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EMC10 | ENST00000334976.11 | c.70C>T | p.Arg24* | stop_gained | Exon 1 of 7 | 1 | NM_206538.4 | ENSP00000334037.6 | ||
GARIN5A | ENST00000600100.6 | c.-226G>A | 5_prime_UTR_variant | Exon 1 of 5 | 1 | NM_001308429.2 | ENSP00000472421.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000585 AC: 1AN: 170814Hom.: 0 AF XY: 0.0000105 AC XY: 1AN XY: 94856
GnomAD4 exome AF: 0.00000284 AC: 4AN: 1408606Hom.: 0 Cov.: 32 AF XY: 0.00000430 AC XY: 3AN XY: 697422
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with dysmorphic facies and variable seizures Pathogenic:1
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000058, PM2). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -
EMC10-related disorder Pathogenic:1
The EMC10 c.70C>T variant is predicted to result in premature protein termination (p.Arg24*). To our knowledge this variant has not been reported in the literature. This variant is reported in 1 out ~171,000 of alleles in individuals in gnomAD (Other Population). Nonsense variants in EMC10 are expected to be pathogenic. This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at