chr20-2597192-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_080751.3(TMC2):c.1118G>A(p.Ser373Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_080751.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC2 | NM_080751.3 | c.1118G>A | p.Ser373Asn | missense_variant | 10/20 | ENST00000358864.2 | |
TMC2 | XM_005260660.5 | c.1193G>A | p.Ser398Asn | missense_variant | 8/18 | ||
TMC2 | XR_001754152.2 | n.1327G>A | non_coding_transcript_exon_variant | 8/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC2 | ENST00000358864.2 | c.1118G>A | p.Ser373Asn | missense_variant | 10/20 | 1 | NM_080751.3 | P1 | |
TMC2 | ENST00000644205.1 | n.1277G>A | non_coding_transcript_exon_variant | 8/15 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251346Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135838
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461824Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727212
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The c.1118G>A (p.S373N) alteration is located in exon 10 (coding exon 10) of the TMC2 gene. This alteration results from a G to A substitution at nucleotide position 1118, causing the serine (S) at amino acid position 373 to be replaced by an asparagine (N). 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