chr1-19219317-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000477853.6(EMC1):c.2968C>T(p.Arg990Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R990Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000477853.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMC1 | NM_015047.3 | c.2968C>T | p.Arg990Trp | missense_variant | 23/23 | ENST00000477853.6 | NP_055862.1 | |
EMC1-AS1 | NR_135114.1 | n.174+8758G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EMC1 | ENST00000477853.6 | c.2968C>T | p.Arg990Trp | missense_variant | 23/23 | 1 | NM_015047.3 | ENSP00000420608 | P4 | |
EMC1-AS1 | ENST00000437898.3 | n.212+8758G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251424Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135894
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727230
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 07, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 990 of the EMC1 protein (p.Arg990Trp). This variant is present in population databases (rs755567367, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EMC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1367729). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EMC1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at