6-3137464-G-A

Position:

• chr6-3137464-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004332.4(BPHL):​c.635G>A​(p.Gly212Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BPHL NM_004332.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32

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]

BPHL (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPHL	NM_004332.4	c.635G>A	p.Gly212Asp	missense_variant	5/7	ENST00000380379.10	NP_004323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPHL	ENST00000380379.10	c.635G>A	p.Gly212Asp	missense_variant	5/7	1	NM_004332.4	ENSP00000369739.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.635G>A (p.G212D) alteration is located in exon 5 (coding exon 5) of the BPHL gene. This alteration results from a G to A substitution at nucleotide position 635, causing the glycine (G) at amino acid position 212 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	.;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.8	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.64
MutPred		0.67		.;Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.82
MPC		0.67
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-3137698;