chr12-120312998-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012240.3(SIRT4):c.907C>T(p.Arg303Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R303H) has been classified as Uncertain significance.
Frequency
Consequence
NM_012240.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIRT4 | NM_012240.3 | c.907C>T | p.Arg303Cys | missense_variant | 4/4 | ENST00000202967.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIRT4 | ENST00000202967.4 | c.907C>T | p.Arg303Cys | missense_variant | 4/4 | 1 | NM_012240.3 | P1 | |
SIRT4 | ENST00000537892.1 | n.461C>T | non_coding_transcript_exon_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251490Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135920
GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 727248
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74440
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2023 | The c.907C>T (p.R303C) alteration is located in exon 4 (coding exon 3) of the SIRT4 gene. This alteration results from a C to T substitution at nucleotide position 907, causing the arginine (R) at amino acid position 303 to be replaced by a cysteine (C). 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