NM_012342.3:c.626C>T

Variant names:

• chr10-28682244-C-T
• NM_012342.3:c.626C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012342.3(BAMBI):​c.626C>T​(p.Ala209Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BAMBI NM_012342.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

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.626C>T	p.Ala209Val	missense	Exon 3 of 3	NP_036474.1	Q13145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAMBI	ENST00000375533.6	TSL:1 MANE Select	c.626C>T	p.Ala209Val	missense	Exon 3 of 3	ENSP00000364683.3	Q13145
	BAMBI	ENST00000913233.1		c.620C>T	p.Ala207Val	missense	Exon 3 of 3	ENSP00000583292.1
	BAMBI	ENST00000963594.1		c.338C>T	p.Ala113Val	missense	Exon 2 of 2	ENSP00000633653.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0057	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.97	L
PhyloP100		7.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.23
Sift	Benign	0.21	T
Sift4G	Benign	0.53	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.64		Gain of methylation at K210 (P = 0.0373)
MVP		0.68
MPC		0.50
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.63
Mutation Taster		=33/67	disease causing

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

hg19: chr10-28971173;