22-32431359-A-C

Position:

• chr22-32431359-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_174932.3(BPIFC):​c.1205T>G​(p.Leu402Trp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: BPIFC NM_174932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFC	NM_174932.3	c.1205T>G	p.Leu402Trp	missense_variant	13/17	ENST00000300399.9	NP_777592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFC	ENST00000300399.9	c.1205T>G	p.Leu402Trp	missense_variant	13/17	1	NM_174932.3	ENSP00000300399.3
BPIFC	ENST00000397452.5	c.1205T>G	p.Leu402Trp	missense_variant	12/16	5		ENSP00000380594.1
BPIFC	ENST00000534972.4	n.*739T>G		non_coding_transcript_exon_variant	11/15	5		ENSP00000439123.3
BPIFC	ENST00000534972.4	n.*739T>G		3_prime_UTR_variant	11/15	5		ENSP00000439123.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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

Nov 25, 2024

The c.1205T>G (p.L402W) alteration is located in exon 11 (coding exon 11) of the BPIFC gene. This alteration results from a T to G substitution at nucleotide position 1205, causing the leucine (L) at amino acid position 402 to be replaced by a tryptophan (W). 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	0.82
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.069	T;.;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T;.
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.9	M;.;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.1	D;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.89
MutPred		0.72		Gain of MoRF binding (P = 0.0309);.;Gain of MoRF binding (P = 0.0309);
MVP		0.52
MPC		0.50
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.88
gMVP		0.81

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: chr22-32827346;