chr6-3152528-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004332.4(BPHL):c.829C>T(p.Arg277Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,612,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
BPHL
NM_004332.4 missense
NM_004332.4 missense
Scores
4
8
4
Clinical Significance
Conservation
PhyloP100: 2.29
Genes affected
BPHL (HGNC:1094): (biphenyl hydrolase like) This gene encodes a member of the serine protease family of hydrolytic enzymes which contain a serine in their active site. The encoded protein may play a role in activation of the antiviral prodrug valacyclovir. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BPHL | NM_004332.4 | c.829C>T | p.Arg277Cys | missense_variant | 7/7 | ENST00000380379.10 | |
BPHL | NM_001302777.1 | c.778C>T | p.Arg260Cys | missense_variant | 8/8 | ||
BPHL | NR_026648.2 | n.1490C>T | non_coding_transcript_exon_variant | 9/9 | |||
BPHL | NR_026649.2 | n.1262C>T | non_coding_transcript_exon_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BPHL | ENST00000380379.10 | c.829C>T | p.Arg277Cys | missense_variant | 7/7 | 1 | NM_004332.4 | P1 | |
ENST00000447644.1 | n.535G>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151892Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000164 AC: 41AN: 250284Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135294
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GnomAD4 exome AF: 0.0000582 AC: 85AN: 1460752Hom.: 0 Cov.: 30 AF XY: 0.0000633 AC XY: 46AN XY: 726616
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2023 | The c.829C>T (p.R277C) alteration is located in exon 7 (coding exon 7) of the BPHL gene. This alteration results from a C to T substitution at nucleotide position 829, causing the arginine (R) at amino acid position 277 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
0.67
.;Loss of disorder (P = 0.0495);.;
MVP
MPC
0.85
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 10
Find out detailed SpliceAI scores and Pangolin per-transcript scores at