chr5-139307411-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_018834.6(MATR3):c.-5C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000422 in 1,612,736 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 (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
MATR3
NM_018834.6 5_prime_UTR
NM_018834.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.15
Genes affected
MATR3 (HGNC:6912): (matrin 3) This gene encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. Mutations of this gene are associated with distal myopathy 2, which often includes vocal cord and pharyngeal weakness. Alternatively spliced transcript variants, including read-through transcripts composed of the upstream small nucleolar RNA host gene 4 (non-protein coding) and matrin 3 gene sequence, have been identified. Pseudogenes of this gene are located on chromosomes 1 and X. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MATR3 | NM_018834.6 | c.-5C>G | 5_prime_UTR_variant | 2/15 | ENST00000394805.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MATR3 | ENST00000394805.8 | c.-5C>G | 5_prime_UTR_variant | 2/15 | 1 | NM_018834.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151874Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249706Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135144
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GnomAD4 exome AF: 0.0000452 AC: 66AN: 1460862Hom.: 0 Cov.: 34 AF XY: 0.0000495 AC XY: 36AN XY: 726800
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis type 21 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
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