20-33217574-G-T

Variant names:

• chr20-33217574-G-T
• rs542232342
• NM_178466.5:c.38G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178466.5(BPIFA3):​c.38G>T​(p.Gly13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G13E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPIFA3 NM_178466.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 0 publications found

Genes affected

BPIFA3 (HGNC:16204): (BPI fold containing family A member 3) Predicted to enable lipid binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178466.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFA3	NM_178466.5	MANE Select	c.38G>T	p.Gly13Val	missense	Exon 1 of 7	NP_848561.2	Q9BQP9-1
	BPIFA3	NM_001042439.2		c.38G>T	p.Gly13Val	missense	Exon 1 of 6	NP_001035904.1	Q9BQP9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFA3	ENST00000375454.8	TSL:5 MANE Select	c.38G>T	p.Gly13Val	missense	Exon 1 of 7	ENSP00000364603.3	Q9BQP9-1
	BPIFA3	ENST00000375452.3	TSL:1	c.38G>T	p.Gly13Val	missense	Exon 1 of 6	ENSP00000364601.3	Q9BQP9-2
	BPIFA3	ENST00000490499.5	TSL:1	n.265G>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.8
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0075	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.13
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.074
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.022	D
Polyphen		0.39	B
Vest4		0.25
MutPred		0.80		Gain of helix (P = 0.0854)
MVP		0.16
MPC		0.031
ClinPred		0.68	D
GERP RS		0.17
PromoterAI		0.0011	Neutral
Varity_R		0.12
gMVP		0.55
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs542232342; hg19: chr20-31805380;