20-45222255-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003008.3(SEMG2):c.623G>A(p.Arg208His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,978 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R208C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003008.3 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 |
---|---|---|---|---|---|---|---|
SEMG2 | NM_003008.3 | c.623G>A | p.Arg208His | missense_variant | 2/3 | ENST00000372769.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMG2 | ENST00000372769.4 | c.623G>A | p.Arg208His | missense_variant | 2/3 | 1 | NM_003008.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251164Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135748
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461802Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 727194
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.623G>A (p.R208H) alteration is located in exon 2 (coding exon 2) of the SEMG2 gene. This alteration results from a G to A substitution at nucleotide position 623, causing the arginine (R) at amino acid position 208 to be replaced by a histidine (H). 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