19-48333372-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_018273.4(TMEM143):c.1227G>T(p.Glu409Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E409A) has been classified as Uncertain significance.
Frequency
Consequence
NM_018273.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM143 | ENST00000293261.8 | c.1227G>T | p.Glu409Asp | missense_variant | Exon 8 of 8 | 1 | NM_018273.4 | ENSP00000293261.2 | ||
TMEM143 | ENST00000377431.6 | c.927G>T | p.Glu309Asp | missense_variant | Exon 6 of 6 | 1 | ENSP00000366649.1 | |||
TMEM143 | ENST00000435956.7 | c.1122G>T | p.Glu374Asp | missense_variant | Exon 7 of 7 | 2 | ENSP00000397038.2 | |||
TMEM143 | ENST00000600816.1 | n.714G>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1456714Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724720
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.