chr15-74902784-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP3_Moderate
The ENST00000562698.5(FAM219B):c.430-1G>C variant causes a splice acceptor change. The variant allele was found at a frequency of 0.0000305 in 1,607,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000562698.5 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAM219B | NM_020447.5 | c.432G>C | p.Gln144His | missense_variant, splice_region_variant | 5/5 | ENST00000357635.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM219B | ENST00000357635.10 | c.432G>C | p.Gln144His | missense_variant, splice_region_variant | 5/5 | 1 | NM_020447.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000817 AC: 2AN: 244934Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132542
GnomAD4 exome AF: 0.0000316 AC: 46AN: 1454916Hom.: 0 Cov.: 31 AF XY: 0.0000304 AC XY: 22AN XY: 723380
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | The c.432G>C (p.Q144H) alteration is located in exon 5 (coding exon 5) of the FAM219B gene. This alteration results from a G to C substitution at nucleotide position 432, causing the glutamine (Q) at amino acid position 144 to be replaced by a histidine (H). 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