chr6-3152559-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004332.4(BPHL):c.860A>T(p.Glu287Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000998 in 1,613,288 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
BPHL
NM_004332.4 missense
NM_004332.4 missense
Scores
1
6
9
Clinical Significance
Conservation
PhyloP100: 7.03
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2764696).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BPHL | NM_004332.4 | c.860A>T | p.Glu287Val | missense_variant | 7/7 | ENST00000380379.10 | |
BPHL | NM_001302777.1 | c.809A>T | p.Glu270Val | missense_variant | 8/8 | ||
BPHL | NR_026648.2 | n.1521A>T | non_coding_transcript_exon_variant | 9/9 | |||
BPHL | NR_026649.2 | n.1293A>T | non_coding_transcript_exon_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BPHL | ENST00000380379.10 | c.860A>T | p.Glu287Val | missense_variant | 7/7 | 1 | NM_004332.4 | P1 | |
ENST00000447644.1 | n.504T>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152082Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250532Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135458
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GnomAD4 exome AF: 0.000107 AC: 157AN: 1461206Hom.: 0 Cov.: 30 AF XY: 0.0000963 AC XY: 70AN XY: 726898
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74278
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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 | Aug 08, 2022 | The c.860A>T (p.E287V) alteration is located in exon 7 (coding exon 7) of the BPHL gene. This alteration results from a A to T substitution at nucleotide position 860, causing the glutamic acid (E) at amino acid position 287 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
0.31
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at