rs1057520160
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_172250.3(MMAA):c.1142C>T(p.Thr381Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_172250.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAA | NM_172250.3 | c.1142C>T | p.Thr381Ile | missense_variant | 7/7 | ENST00000649156.2 | |
MMAA | NM_001375644.1 | c.1142C>T | p.Thr381Ile | missense_variant | 7/7 | ||
MMAA | XM_011531684.4 | c.1142C>T | p.Thr381Ile | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAA | ENST00000649156.2 | c.1142C>T | p.Thr381Ile | missense_variant | 7/7 | NM_172250.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Methylmalonic aciduria, cblA type Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 381 of the MMAA protein (p.Thr381Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MMAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 377200). 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 not expected to disrupt MMAA 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 04, 2020 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 08, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Sep 23, 2022 | The MMAA c.1142C>T (p.Thr381Ile) missense variant results in the substitution of threonine at amino acid position 381 with isoleucine. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.1142C>T (p.Thr381Ile) variant is classified as a variant of uncertain significance for methylmalonic aciduria, cblA type. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2021 | The c.1142C>T (p.T381I) alteration is located in exon 7 (coding exon 6) of the MMAA gene. This alteration results from a C to T substitution at nucleotide position 1142, causing the threonine (T) at amino acid position 381 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at