6-3118751-T-G

Position:

• chr6-3118751-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004332.4(BPHL):​c.11T>G​(p.Val4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000541 in 1,109,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: BPHL NM_004332.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.46

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057235777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPHL	NM_004332.4	c.11T>G	p.Val4Gly	missense_variant	1/7	ENST00000380379.10	NP_004323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPHL	ENST00000380379.10	c.11T>G	p.Val4Gly	missense_variant	1/7	1	NM_004332.4	ENSP00000369739.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000541 AC: 6 AN: 1109012 Hom.: 0 Cov.: 32 AF XY: 0.00000569 AC XY: 3 AN XY: 527004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000168

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000449

GnomAD4 genome Cov.: 33

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

May 06, 2024

The c.11T>G (p.V4G) alteration is located in exon 1 (coding exon 1) of the BPHL gene. This alteration results from a T to G substitution at nucleotide position 11, causing the valine (V) at amino acid position 4 to be replaced by a glycine (G). 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	Benign	0.060
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.21
DANN	Benign	0.43
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.024
Sift	Benign	0.50	T
Sift4G	Uncertain	0.027	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.39		Loss of sheet (P = 0.0025);
MVP		0.088
MPC		0.26
ClinPred		0.16	T
GERP RS		-3.8
Varity_R		0.052
gMVP		0.53

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: chr6-3118985;