chr22-42397952-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_145912.8(NFAM1):c.569G>A(p.Arg190Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,588,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R190W) has been classified as Uncertain significance.
Frequency
Consequence
NM_145912.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NFAM1 | NM_145912.8 | c.569G>A | p.Arg190Gln | missense_variant | Exon 4 of 6 | ENST00000329021.10 | NP_666017.1 | |
NFAM1 | NM_001371362.1 | c.413G>A | p.Arg138Gln | missense_variant | Exon 6 of 8 | NP_001358291.1 | ||
NFAM1 | NM_001318323.3 | c.456G>A | p.Ala152Ala | synonymous_variant | Exon 3 of 5 | NP_001305252.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000169 AC: 4AN: 236378Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 127852
GnomAD4 exome AF: 0.0000188 AC: 27AN: 1435932Hom.: 0 Cov.: 27 AF XY: 0.0000168 AC XY: 12AN XY: 714822
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at