12-27495843-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001395208.2(SMCO2):c.821G>A(p.Arg274His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,509,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001395208.2 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 |
---|---|---|---|---|---|---|---|
SMCO2 | NM_001395208.2 | c.821G>A | p.Arg274His | missense_variant | 8/9 | ENST00000535986.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCO2 | ENST00000535986.2 | c.821G>A | p.Arg274His | missense_variant | 8/9 | 5 | NM_001395208.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000666 AC: 1AN: 150088Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000131 AC: 2AN: 152790Hom.: 0 AF XY: 0.0000247 AC XY: 2AN XY: 80846
GnomAD4 exome AF: 0.0000140 AC: 19AN: 1359838Hom.: 0 Cov.: 31 AF XY: 0.00000900 AC XY: 6AN XY: 666638
GnomAD4 genome ? AF: 0.00000666 AC: 1AN: 150088Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.821G>A (p.R274H) alteration is located in exon 8 (coding exon 7) of the SMCO2 gene. This alteration results from a G to A substitution at nucleotide position 821, causing the arginine (R) at amino acid position 274 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