chr19-4175062-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016539.4(SIRT6):c.704G>A(p.Arg235His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,587,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/15 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. R235C) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIRT6 | NM_016539.4 | c.704G>A | p.Arg235His | missense_variant | 7/8 | ENST00000337491.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIRT6 | ENST00000337491.7 | c.704G>A | p.Arg235His | missense_variant | 7/8 | 1 | NM_016539.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152106Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000352 AC: 7AN: 198968Hom.: 0 AF XY: 0.00000925 AC XY: 1AN XY: 108058
GnomAD4 exome AF: 0.0000160 AC: 23AN: 1435230Hom.: 0 Cov.: 34 AF XY: 0.0000112 AC XY: 8AN XY: 711976
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.000162 AC XY: 12AN XY: 74302
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.704G>A (p.R235H) alteration is located in exon 7 (coding exon 7) of the SIRT6 gene. This alteration results from a G to A substitution at nucleotide position 704, causing the arginine (R) at amino acid position 235 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