chr16-1338667-G-A

Variant names:

• chr16-1338667-G-A
• rs761781931
• NM_001199097.2:c.118G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199097.2(BAIAP3):​c.118G>A​(p.Ala40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A40S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: BAIAP3 NM_001199097.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04854417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP3	NM_001199097.2	c.118G>A	p.Ala40Thr	missense_variant	Exon 2 of 34	ENST00000426824.8	NP_001186026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAIAP3	ENST00000426824.8	c.118G>A	p.Ala40Thr	missense_variant	Exon 2 of 34	2	NM_001199097.2	ENSP00000407242.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431104 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 709506

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

African (AFR) AF: 0.00 AC: 0 AN: 32950

American (AMR) AF: 0.00 AC: 0 AN: 39794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25568

East Asian (EAS) AF: 0.00 AC: 0 AN: 38350

South Asian (SAS) AF: 0.00 AC: 0 AN: 83036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4592

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098622

Other (OTH) AF: 0.00 AC: 0 AN: 59102

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.84
DEOGEN2	Benign	0.017	.;.;.;.;T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.67	T;.;T;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.049	T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	.;.;.;.;N;.;.
PhyloP100		-0.30
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.64	N;N;N;N;N;.;N
REVEL	Benign	0.096
Sift	Benign	1.0	T;T;T;T;T;.;T
Sift4G	Benign	0.33	T;T;T;T;T;T;T
Polyphen		0.0010	.;.;.;.;B;.;.
Vest4		0.12
MutPred		0.13		.;.;.;.;Gain of glycosylation at A75 (P = 0.0016);.;.;
MVP		0.54
MPC		0.083
ClinPred		0.048	T
GERP RS		-9.4
Varity_R		0.031
gMVP		0.17
Mutation Taster		=99/1	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

Publications

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Other links and lift over

dbSNP: rs761781931; hg19: chr16-1388668;