11-406440-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001135054.2(SIGIRR):c.978C>A(p.Asp326Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,612,744 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. D326G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001135054.2 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 |
---|---|---|---|---|---|---|---|
SIGIRR | NM_001135054.2 | c.978C>A | p.Asp326Glu | missense_variant | 9/10 | ENST00000431843.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGIRR | ENST00000431843.7 | c.978C>A | p.Asp326Glu | missense_variant | 9/10 | 1 | NM_001135054.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152242Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.0000762 AC: 19AN: 249270Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135388
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1460384Hom.: 0 Cov.: 88 AF XY: 0.0000179 AC XY: 13AN XY: 726474
GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152360Hom.: 1 Cov.: 34 AF XY: 0.000268 AC XY: 20AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2023 | The c.978C>A (p.D326E) alteration is located in exon 9 (coding exon 8) of the SIGIRR gene. This alteration results from a C to A substitution at nucleotide position 978, causing the aspartic acid (D) at amino acid position 326 to be replaced by a glutamic acid (E). 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