16-1346605-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001199097.2(BAIAP3):c.2563G>A(p.Ala855Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. A855P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

BAIAP3
NM_001199097.2 missense, splice_region

Scores

Splicing: ADA: 0.9994

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

0 publications found

Variant links:

Genes affected

BAIAP3 (HGNC:948): (BAI1 associated protein 3) This p53-target gene encodes a brain-specific angiogenesis inhibitor. The protein is a seven-span transmembrane protein and a member of the secretin receptor family. It interacts with the cytoplasmic region of brain-specific angiogenesis inhibitor 1. This protein also contains two C2 domains, which are often found in proteins involved in signal transduction or membrane trafficking. Its expression pattern and similarity to other proteins suggest that it may be involved in synaptic functions. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

BAIAP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199097.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAIAP3	NM_001199097.2	MANE Select	c.2563G>A	p.Ala855Thr	missense splice_region	Exon 27 of 34	NP_001186026.1	O94812-6
BAIAP3	NM_003933.5		c.2668G>A	p.Ala890Thr	missense splice_region	Exon 27 of 34	NP_003924.2
BAIAP3	NM_001286464.2		c.2614G>A	p.Ala872Thr	missense splice_region	Exon 27 of 34	NP_001273393.2	O94812-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAIAP3	ENST00000426824.8	TSL:2 MANE Select	c.2563G>A	p.Ala855Thr	missense splice_region	Exon 27 of 34	ENSP00000407242.4	O94812-6
BAIAP3	ENST00000324385.9	TSL:1	c.2668G>A	p.Ala890Thr	missense splice_region	Exon 27 of 34	ENSP00000324510.5	O94812-1
BAIAP3	ENST00000397488.6	TSL:1	c.2614G>A	p.Ala872Thr	missense splice_region	Exon 27 of 34	ENSP00000380625.2	O94812-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1403634

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693100

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32018

American (AMR)

AF:

0.00

AC:

AN:

36228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25240

East Asian (EAS)

AF:

0.00

AC:

AN:

36384

South Asian (SAS)

AF:

0.00

AC:

AN:

79930

European-Finnish (FIN)

AF:

0.0000213

AC:

AN:

47030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082840

Other (OTH)

AF:

0.00

AC:

AN:

58270

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.6

PhyloP100

1.3

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.65

MutPred

0.67

Gain of phosphorylation at A890 (P = 0.1548)

MVP

0.90

MPC

0.46

ClinPred

0.99

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.83

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over