22-32435835-G-A

Position:

• chr22-32435835-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174932.3(BPIFC):​c.793C>T​(p.Pro265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPIFC NM_174932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.794

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15158948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFC	NM_174932.3	c.793C>T	p.Pro265Ser	missense_variant	10/17	ENST00000300399.9	NP_777592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFC	ENST00000300399.9	c.793C>T	p.Pro265Ser	missense_variant	10/17	1	NM_174932.3	ENSP00000300399.3
BPIFC	ENST00000397452.5	c.793C>T	p.Pro265Ser	missense_variant	9/16	5		ENSP00000380594.1
BPIFC	ENST00000534972.4	n.*498C>T		non_coding_transcript_exon_variant	9/15	5		ENSP00000439123.3
BPIFC	ENST00000534972.4	n.*498C>T		3_prime_UTR_variant	9/15	5		ENSP00000439123.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 01, 2024

The c.793C>T (p.P265S) alteration is located in exon 8 (coding exon 8) of the BPIFC gene. This alteration results from a C to T substitution at nucleotide position 793, causing the proline (P) at amino acid position 265 to be replaced by a serine (S). 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	0.098
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.73	T;T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;L
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-6.3	D;.;D
REVEL	Benign	0.10
Sift	Benign	0.059	T;.;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.099	B;.;B
Vest4		0.081
MutPred		0.52		Loss of glycosylation at S264 (P = 0.0801);.;Loss of glycosylation at S264 (P = 0.0801);
MVP		0.16
MPC		0.11
ClinPred		0.87	D
GERP RS		4.6
Varity_R		0.25
gMVP		0.67

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: chr22-32831822;