1-160030779-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_145167.3(PIGM):āc.961A>Gā(p.Thr321Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T321K) has been classified as Uncertain significance.
Frequency
Consequence
NM_145167.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251458Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135904
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461846Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727222
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2023 | The c.961A>G (p.T321A) alteration is located in exon 1 (coding exon 1) of the PIGM gene. This alteration results from a A to G substitution at nucleotide position 961, causing the threonine (T) at amino acid position 321 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2017 | The T321A variant in the PIGM gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T321A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T321A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T321A as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at