chr19-43486610-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198850.4(PHLDB3):c.1427G>A(p.Arg476Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,612,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_198850.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHLDB3 | NM_198850.4 | c.1427G>A | p.Arg476Gln | missense_variant, splice_region_variant | 12/16 | ENST00000292140.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHLDB3 | ENST00000292140.10 | c.1427G>A | p.Arg476Gln | missense_variant, splice_region_variant | 12/16 | 5 | NM_198850.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000102 AC: 25AN: 245152Hom.: 0 AF XY: 0.0000975 AC XY: 13AN XY: 133340
GnomAD4 exome AF: 0.000120 AC: 175AN: 1459912Hom.: 0 Cov.: 32 AF XY: 0.0000991 AC XY: 72AN XY: 726202
GnomAD4 genome AF: 0.000138 AC: 21AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74448
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.1427G>A (p.R476Q) alteration is located in exon 12 (coding exon 11) of the PHLDB3 gene. This alteration results from a G to A substitution at nucleotide position 1427, causing the arginine (R) at amino acid position 476 to be replaced by a glutamine (Q). 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