12-27501975-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001395208.2(SMCO2):c.886C>T(p.Leu296Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000788 in 1,396,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. L296V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001395208.2 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 |
---|---|---|---|---|---|---|---|
SMCO2 | NM_001395208.2 | c.886C>T | p.Leu296Phe | missense_variant | 9/9 | ENST00000535986.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCO2 | ENST00000535986.2 | c.886C>T | p.Leu296Phe | missense_variant | 9/9 | 5 | NM_001395208.2 | ||
SMCO2 | ENST00000298876.8 | c.736C>T | p.Leu246Phe | missense_variant | 8/8 | 5 | P1 | ||
SMCO2 | ENST00000698358.1 | c.499C>T | p.Leu167Phe | missense_variant | 6/6 | ||||
SMCO2 | ENST00000541168.1 | n.750C>T | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000513 AC: 8AN: 155832Hom.: 0 AF XY: 0.0000485 AC XY: 4AN XY: 82522
GnomAD4 exome AF: 0.00000788 AC: 11AN: 1396560Hom.: 0 Cov.: 31 AF XY: 0.0000116 AC XY: 8AN XY: 688848
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2023 | The c.886C>T (p.L296F) alteration is located in exon 9 (coding exon 8) of the SMCO2 gene. This alteration results from a C to T substitution at nucleotide position 886, causing the leucine (L) at amino acid position 296 to be replaced by a phenylalanine (F). 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