chr5-139294029-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PVS1_ModeratePP3BS2
The ENST00000618441.5(MATR3):c.-178+1G>T variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000797 in 1,279,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000618441.5 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MATR3 | NM_018834.6 | c.-178+224G>T | intron_variant | ENST00000394805.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MATR3 | ENST00000394805.8 | c.-178+224G>T | intron_variant | 1 | NM_018834.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000272 AC: 5AN: 18378Hom.: 0 AF XY: 0.000281 AC XY: 3AN XY: 10678
GnomAD4 exome AF: 0.0000781 AC: 88AN: 1127018Hom.: 0 Cov.: 30 AF XY: 0.0000722 AC XY: 39AN XY: 540356
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74376
ClinVar
Submissions by phenotype
MATR3-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 15, 2023 | The MATR3 c.48+1G>T variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in one sporadic amyotrophic lateral sclerosis case and has been shown to alter splicing (Leblond et al. 2016. PubMed ID: 26493020). However other isoforms of this gene do not utilize this splice site. This variant is reported in 0.025% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-138629718-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at