4-73492035-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.1007G>A(p.Ser336Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,104 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.1007G>A | p.Ser336Asn | missense_variant | 8/15 | ENST00000226355.5 | |
AFM | XM_017007842.3 | c.1007G>A | p.Ser336Asn | missense_variant | 8/13 | ||
AFM | XM_017007843.3 | c.1007G>A | p.Ser336Asn | missense_variant | 8/11 | ||
AFM | XM_017007844.3 | c.1007G>A | p.Ser336Asn | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFM | ENST00000226355.5 | c.1007G>A | p.Ser336Asn | missense_variant | 8/15 | 1 | NM_001133.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250036Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135116
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460880Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726684
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2023 | The c.1007G>A (p.S336N) 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 1007, causing the serine (S) at amino acid position 336 to be replaced by an asparagine (N). 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