12-50350357-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001145475.3(FAM186A):āc.6475A>Gā(p.Ile2159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,550,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001145475.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FAM186A | ENST00000327337.6 | c.6475A>G | p.Ile2159Val | missense_variant | 4/8 | 5 | NM_001145475.3 | ENSP00000329995.5 | ||
FAM186A | ENST00000543111.5 | c.6475A>G | p.Ile2159Val | missense_variant | 4/8 | 5 | ENSP00000441337.1 | |||
FAM186A | ENST00000543096.5 | c.508A>G | p.Ile170Val | missense_variant | 1/5 | 2 | ENSP00000443703.1 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 151578Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000652 AC: 1AN: 153300Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 81260
GnomAD4 exome AF: 0.0000164 AC: 23AN: 1398380Hom.: 0 Cov.: 44 AF XY: 0.0000116 AC XY: 8AN XY: 689700
GnomAD4 genome AF: 0.000191 AC: 29AN: 151696Hom.: 0 Cov.: 30 AF XY: 0.000176 AC XY: 13AN XY: 74048
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 26, 2023 | The c.6475A>G (p.I2159V) alteration is located in exon 4 (coding exon 4) of the FAM186A gene. This alteration results from a A to G substitution at nucleotide position 6475, causing the isoleucine (I) at amino acid position 2159 to be replaced by a valine (V). 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