Genetic Variant TRABD2B:p.Asp400Asn (chr1-47775321-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001194986.2(TRABD2B):c.1198G>A(p.Asp400Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000198 in 1,246,028 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 (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TRABD2B
NM_001194986.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037205607).

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.1198G>A	p.Asp400Asn	missense	Exon 6 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.1198G>A	p.Asp400Asn	missense	Exon 6 of 7	ENSP00000476820.1	A6NFA1
TRABD2B	ENST00000878673.1		c.1303G>A	p.Asp435Asn	missense	Exon 7 of 8	ENSP00000548732.1
TRABD2B	ENST00000878672.1		c.1051G>A	p.Asp351Asn	missense	Exon 5 of 6	ENSP00000548731.1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000281

AC:

AN:

10690

AF XY:

0.000555

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000287

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

208

AN:

1093716

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

108

AN XY:

518246

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

23314

American (AMR)

AF:

0.000531

AC:

AN:

9422

Ashkenazi Jewish (ASJ)

AF:

0.0000683

AC:

AN:

14652

East Asian (EAS)

AF:

0.00

AC:

AN:

26872

South Asian (SAS)

AF:

0.00

AC:

AN:

23814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22396

Middle Eastern (MID)

AF:

0.00229

AC:

AN:

3930

European-Non Finnish (NFE)

AF:

0.000184

AC:

170

AN:

925050

Other (OTH)

AF:

0.000452

AC:

AN:

44266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

AF:

0.000256

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41582

American (AMR)

AF:

0.000261

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000438

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000573

AC:

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

0.078

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.037

MutationAssessor

Benign

0.0

PhyloP100

4.5

PrimateAI

Uncertain

0.52

Sift4G

Benign

0.45

Vest4

0.14

MVP

0.15

MPC

0.90

GERP RS

5.1

Varity_R

0.050

gMVP

0.15

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over