10-70255598-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_022146.5(NPFFR1):c.652A>G(p.Thr218Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,557,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. T218I) has been classified as Uncertain significance.
Frequency
Consequence
NM_022146.5 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 |
---|---|---|---|---|---|---|---|
NPFFR1 | NM_022146.5 | c.652A>G | p.Thr218Ala | missense_variant | 4/4 | ENST00000277942.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPFFR1 | ENST00000277942.7 | c.652A>G | p.Thr218Ala | missense_variant | 4/4 | 5 | NM_022146.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000987 AC: 15AN: 151912Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000617 AC: 1AN: 162086Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 86560
GnomAD4 exome AF: 0.00000854 AC: 12AN: 1405412Hom.: 0 Cov.: 40 AF XY: 0.0000101 AC XY: 7AN XY: 693796
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152030Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74328
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | 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