Genetic Variant NM_012342.3:c.416T>A (chr10-28682034-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_012342.3(BAMBI):c.416T>A(p.Val139Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BAMBI
NM_012342.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62

Publications

0 publications found

Variant links:

Genes affected

BAMBI (HGNC:30251): (BMP and activin membrane bound inhibitor) This gene encodes a transmembrane glycoprotein related to the type I receptors of the transforming growth factor-beta (TGF-beta) family, whose members play important roles in signal transduction in many developmental and pathological processes. The encoded protein however is a pseudoreceptor, lacking an intracellular serine/threonine kinase domain required for signaling. Similar proteins in frog, mouse and zebrafish function as negative regulators of TGF-beta, which has led to the suggestion that the encoded protein may function to limit the signaling range of the TGF-beta family during early embryogenesis. [provided by RefSeq, Jul 2008]

BAMBI links:

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ACMG classification

Classification was made for transcript

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_012342.3. 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
	BAMBI	NM_012342.3	MANE Select	c.416T>A	p.Val139Glu	missense	Exon 3 of 3	NP_036474.1	Q13145

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAMBI	ENST00000375533.6	TSL:1 MANE Select	c.416T>A	p.Val139Glu	missense	Exon 3 of 3	ENSP00000364683.3	Q13145
BAMBI	ENST00000913233.1		c.410T>A	p.Val137Glu	missense	Exon 3 of 3	ENSP00000583292.1
BAMBI	ENST00000963594.1		c.128T>A	p.Val43Glu	missense	Exon 2 of 2	ENSP00000633653.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

M_CAP

Benign

0.0054

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.90

PhyloP100

7.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.32

Sift

Benign

0.042

Sift4G

Uncertain

0.046

Polyphen

0.48

Vest4

0.75

MutPred

0.50

Gain of disorder (P = 0.0018)

MVP

0.67

MPC

0.21

ClinPred

0.74

GERP RS

5.9

Varity_R

0.45

gMVP

0.74

Mutation Taster

=28/72

disease causing

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over