chr19-4175063-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_016539.4(SIRT6):c.703C>T(p.Arg235Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,588,628 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. R235H) has been classified as Uncertain significance.
Frequency
Consequence
NM_016539.4 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 |
---|---|---|---|---|---|---|---|
SIRT6 | NM_016539.4 | c.703C>T | p.Arg235Cys | missense_variant | 7/8 | ENST00000337491.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIRT6 | ENST00000337491.7 | c.703C>T | p.Arg235Cys | missense_variant | 7/8 | 1 | NM_016539.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000149 AC: 3AN: 201094Hom.: 0 AF XY: 0.00000915 AC XY: 1AN XY: 109260
GnomAD4 exome AF: 0.0000125 AC: 18AN: 1436504Hom.: 0 Cov.: 34 AF XY: 0.0000140 AC XY: 10AN XY: 712724
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74296
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.703C>T (p.R235C) alteration is located in exon 7 (coding exon 7) of the SIRT6 gene. This alteration results from a C to T substitution at nucleotide position 703, causing the arginine (R) at amino acid position 235 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