14-94309801-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001756.4(SERPINA6):c.819G>A(p.Met273Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001756.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINA6 | NM_001756.4 | c.819G>A | p.Met273Ile | missense_variant | Exon 3 of 5 | ENST00000341584.4 | NP_001747.3 | |
SERPINA6 | XM_047431827.1 | c.990G>A | p.Met330Ile | missense_variant | Exon 3 of 5 | XP_047287783.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SERPINA6 | ENST00000341584.4 | c.819G>A | p.Met273Ile | missense_variant | Exon 3 of 5 | 1 | NM_001756.4 | ENSP00000342850.3 | ||
SERPINA6 | ENST00000555056.1 | n.*131G>A | non_coding_transcript_exon_variant | Exon 3 of 5 | 2 | ENSP00000451045.1 | ||||
SERPINA6 | ENST00000555056.1 | n.*131G>A | 3_prime_UTR_variant | Exon 3 of 5 | 2 | ENSP00000451045.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251276Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135810
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.819G>A (p.M273I) alteration is located in exon 3 (coding exon 2) of the SERPINA6 gene. This alteration results from a G to A substitution at nucleotide position 819, causing the methionine (M) at amino acid position 273 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
The M273I variant in the SERPINA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M273I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M273I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret M273I as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at