Variant chr22-32433729-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174932.3(BPIFC):c.968T>G(p.Val323Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

BPIFC
NM_174932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

BPIFC (HGNC:16503): (BPI fold containing family C) Predicted to enable lipid binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BPIFC links:

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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	Protein	UniProt
BPIFC	NM_174932.3 linkuse as main transcript	c.968T>G	p.Val323Gly	missense_variant	11/17	ENST00000300399.9	NP_777592.1	Q8NFQ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BPIFC	ENST00000300399.9 linkuse as main transcript	c.968T>G	p.Val323Gly	missense_variant	11/17	1	NM_174932.3	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5 linkuse as main transcript	c.968T>G	p.Val323Gly	missense_variant	10/16	5		ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4 linkuse as main transcript	n.*673T>G		non_coding_transcript_exon_variant	10/15	5		ENSP00000439123.3	A0A8C8NLL8
BPIFC	ENST00000534972.4 linkuse as main transcript	n.*673T>G		3_prime_UTR_variant	10/15	5		ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251430

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1461680

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000165

AC:

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

Mar 28, 2024

The c.968T>G (p.V323G) alteration is located in exon 9 (coding exon 9) of the BPIFC gene. This alteration results from a T to G substitution at nucleotide position 968, causing the valine (V) at amino acid position 323 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

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.54

T;T;.

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.3

D;.;D

REVEL

Benign

0.26

Sift

Uncertain

0.013

D;.;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.90

P;.;P

Vest4

0.39

MVP

0.51

MPC

0.30

ClinPred

0.55

GERP RS

5.8

Varity_R

0.77

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over