17-28956229-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_178860.5(SEZ6):c.2882G>A(p.Arg961His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,313,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R961C) has been classified as Uncertain significance.
Frequency
Consequence
NM_178860.5 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 |
---|---|---|---|---|---|---|---|
SEZ6 | NM_178860.5 | c.2882G>A | p.Arg961His | missense_variant | 16/17 | ENST00000317338.17 | |
LOC105371716 | XR_001752822.2 | n.1807+2821C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEZ6 | ENST00000317338.17 | c.2882G>A | p.Arg961His | missense_variant | 16/17 | 1 | NM_178860.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000267 AC: 19AN: 71042Hom.: 0 Cov.: 19
GnomAD3 exomes AF: 0.000204 AC: 28AN: 137144Hom.: 0 AF XY: 0.000158 AC XY: 12AN XY: 75838
GnomAD4 exome AF: 0.000412 AC: 512AN: 1242812Hom.: 0 Cov.: 45 AF XY: 0.000406 AC XY: 244AN XY: 601084
GnomAD4 genome ? AF: 0.000267 AC: 19AN: 71042Hom.: 0 Cov.: 19 AF XY: 0.000347 AC XY: 12AN XY: 34584
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2023 | The c.2882G>A (p.R961H) alteration is located in exon 16 (coding exon 16) of the SEZ6 gene. This alteration results from a G to A substitution at nucleotide position 2882, causing the arginine (R) at amino acid position 961 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