16-4340943-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_016069.11(PAM16):c.268G>A(p.Gly90Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,358 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 (★).
Frequency
Consequence
NM_016069.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAM16 | NM_016069.11 | c.268G>A | p.Gly90Ser | missense_variant | Exon 4 of 5 | ENST00000318059.8 | NP_057153.8 | |
CORO7-PAM16 | NM_001201479.2 | c.3037G>A | p.Gly1013Ser | missense_variant | Exon 30 of 31 | NP_001188408.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAM16 | ENST00000318059.8 | c.268G>A | p.Gly90Ser | missense_variant | Exon 4 of 5 | 1 | NM_016069.11 | ENSP00000315693.3 | ||
CORO7-PAM16 | ENST00000572467.5 | c.3037G>A | p.Gly1013Ser | missense_variant | Exon 30 of 31 | 2 | ENSP00000460885.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461358Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726932
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with PAM16-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 90 of the PAM16 protein (p.Gly90Ser). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at