dbSNP rs1236008749: TRABD2B:p.Glu284Gln (chr1-47794724-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001194986.2(TRABD2B):c.850G>C(p.Glu284Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,532,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E284K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

TRABD2B
NM_001194986.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39

Publications

1 publications found

Variant links:

Genes affected

TRABD2B (HGNC:44200): (TraB domain containing 2B) Enables Wnt-protein binding activity and metalloendopeptidase activity. Involved in several processes, including negative regulation of Wnt signaling pathway; positive regulation of protein oxidation; and positive regulation of protein-containing complex assembly. Is integral component of organelle membrane and integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRABD2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27762252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194986.2. 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
	TRABD2B	NM_001194986.2	MANE Select	c.850G>C	p.Glu284Gln	missense	Exon 4 of 7	NP_001181915.1	A6NFA1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRABD2B	ENST00000606738.3	TSL:1 MANE Select	c.850G>C	p.Glu284Gln	missense	Exon 4 of 7	ENSP00000476820.1	A6NFA1
TRABD2B	ENST00000878673.1		c.850G>C	p.Glu284Gln	missense	Exon 4 of 8	ENSP00000548732.1
TRABD2B	ENST00000878672.1		c.703G>C	p.Glu235Gln	missense	Exon 3 of 6	ENSP00000548731.1

Frequencies

GnomAD3 genomes

AF:

0.0000858

AC:

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000854

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000514

AC:

AN:

136232

AF XY:

0.0000946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000288

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000507

AC:

AN:

1381474

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

681658

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31482

American (AMR)

AF:

0.000197

AC:

AN:

35584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25076

East Asian (EAS)

AF:

0.00

AC:

AN:

35530

South Asian (SAS)

AF:

0.00

AC:

AN:

79078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077124

Other (OTH)

AF:

0.00

AC:

AN:

57742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000858

AC:

AN:

151474

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41246

American (AMR)

AF:

0.000854

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67904

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

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

Benign

0.25

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.28

MutationAssessor

Uncertain

2.5

PhyloP100

7.4

PrimateAI

Uncertain

0.75

Sift4G

Benign

0.11

Vest4

0.27

MVP

0.25

MPC

2.0

GERP RS

4.8

Varity_R

0.18

gMVP

0.80

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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