chr4-73492020-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001133.2(AFM):c.992G>A(p.Gly331Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001133.2 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 |
---|---|---|---|---|---|---|---|
AFM | NM_001133.2 | c.992G>A | p.Gly331Glu | missense_variant | 8/15 | ENST00000226355.5 | |
AFM | XM_017007842.3 | c.992G>A | p.Gly331Glu | missense_variant | 8/13 | ||
AFM | XM_017007843.3 | c.992G>A | p.Gly331Glu | missense_variant | 8/11 | ||
AFM | XM_017007844.3 | c.992G>A | p.Gly331Glu | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFM | ENST00000226355.5 | c.992G>A | p.Gly331Glu | missense_variant | 8/15 | 1 | NM_001133.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249892Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134962
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460974Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726712
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The c.992G>A (p.G331E) alteration is located in exon 8 (coding exon 8) of the AFM gene. This alteration results from a G to A substitution at nucleotide position 992, causing the glycine (G) at amino acid position 331 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