chr19-50791683-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_033068.3(ACP4):c.331C>T(p.Arg111Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,613,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_033068.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACP4 | ENST00000270593.2 | c.331C>T | p.Arg111Cys | missense_variant | Exon 4 of 11 | 1 | NM_033068.3 | ENSP00000270593.1 | ||
SMIM47 | ENST00000636757.1 | c.-60+722G>A | intron_variant | Intron 2 of 4 | 5 | ENSP00000489695.1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250636Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135636
GnomAD4 exome AF: 0.0000767 AC: 112AN: 1460898Hom.: 0 Cov.: 31 AF XY: 0.0000853 AC XY: 62AN XY: 726740
GnomAD4 genome AF: 0.000125 AC: 19AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74498
ClinVar
Submissions by phenotype
Amelogenesis imperfecta, type 1J Pathogenic:3
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not provided Pathogenic:1
Published functional studies demonstrate a damaging effect: a knock in mouse model with a homozygous variant homologous to R111C demonstrated incisors and molars with a thin layer of aplastic enamel with many ectopic mineralized nodules (Liang et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 27843125, 36183038) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at