13-99501754-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_004800.3(TM9SF2):āc.148G>Cā(p.Glu50Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,608,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E50V) has been classified as Uncertain significance.
Frequency
Consequence
NM_004800.3 missense
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 |
---|---|---|---|---|---|---|---|
TM9SF2 | NM_004800.3 | c.148G>C | p.Glu50Gln | missense_variant | 1/17 | ENST00000376387.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TM9SF2 | ENST00000376387.5 | c.148G>C | p.Glu50Gln | missense_variant | 1/17 | 1 | NM_004800.3 | P1 | |
TM9SF2 | ENST00000642475.1 | c.148G>C | p.Glu50Gln | missense_variant | 3/19 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000817 AC: 2AN: 244770Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132982
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1456748Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 724880
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2023 | The c.148G>C (p.E50Q) alteration is located in exon 1 (coding exon 1) of the TM9SF2 gene. This alteration results from a G to C substitution at nucleotide position 148, causing the glutamic acid (E) at amino acid position 50 to be replaced by a glutamine (Q). 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