chr2-196847951-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024989.4(PGAP1):c.1948T>A(p.Leu650Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,422,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. L650F) has been classified as Uncertain significance.
Frequency
Consequence
NM_024989.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGAP1 | NM_024989.4 | c.1948T>A | p.Leu650Met | missense_variant | 21/27 | ENST00000354764.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGAP1 | ENST00000354764.9 | c.1948T>A | p.Leu650Met | missense_variant | 21/27 | 1 | NM_024989.4 | P1 | |
PGAP1 | ENST00000423035.5 | c.*1879T>A | 3_prime_UTR_variant, NMD_transcript_variant | 22/28 | 1 | ||||
PGAP1 | ENST00000409475.5 | c.*75T>A | 3_prime_UTR_variant | 20/20 | 2 | ||||
PGAP1 | ENST00000470179.5 | n.1412T>A | non_coding_transcript_exon_variant | 17/22 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000352 AC: 5AN: 1422462Hom.: 0 Cov.: 28 AF XY: 0.00000424 AC XY: 3AN XY: 707518
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 12, 2020 | The c.1948T>A (p.L650M) alteration is located in exon 21 (coding exon 21) of the PGAP1 gene. This alteration results from a T to A substitution at nucleotide position 1948, causing the leucine (L) at amino acid position 650 to be replaced by a methionine (M). 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