rs138516982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003190.5(TAPBP):c.1234G>A(p.Asp412Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000403 in 1,613,762 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

TAPBP
NM_003190.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.08

Publications

3 publications found

Variant links:

Genes affected

TAPBP (HGNC:11566): (TAP binding protein) This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TAPBP Gene-Disease associations (from GenCC):

MHC class I deficiency
Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet
MHC class I deficiency 1
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

TAPBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007776201).

BP6

Variant 6-33304194-C-T is Benign according to our data. Variant chr6-33304194-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 534736.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003190.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAPBP	NM_003190.5	MANE Select	c.1234G>A	p.Asp412Asn	missense	Exon 6 of 8	NP_003181.3
TAPBP	NM_172208.3		c.1234G>A	p.Asp412Asn	missense	Exon 6 of 7	NP_757345.2	A0A0A0MSV9
TAPBP	NM_001410875.1		c.1234G>A	p.Asp412Asn	missense	Exon 6 of 7	NP_001397804.1	A0A8V8TQC5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.1234G>A	p.Asp412Asn	missense	Exon 6 of 8	ENSP00000395701.2	O15533-1
TAPBP	ENST00000426633.6	TSL:1	c.1234G>A	p.Asp412Asn	missense	Exon 6 of 7	ENSP00000404833.2	O15533-3
TAPBP	ENST00000489157.6	TSL:1	c.973G>A	p.Asp325Asn	missense	Exon 5 of 7	ENSP00000419659.1	O15533-4

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00612

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

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:

0.0000294

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.000542

AC:

136

AN:

251036

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.00616

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000253

AC:

370

AN:

1461766

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

160

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00651

AC:

218

AN:

33478

American (AMR)

AF:

0.000939

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1111942

Other (OTH)

AF:

0.000580

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00184

AC:

280

AN:

151996

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00610

AC:

253

AN:

41472

American (AMR)

AF:

0.00151

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67970

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000699

Hom.:

Bravo

AF:

0.00219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000651

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.087

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.049

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.80

PhyloP100

4.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.69

MVP

0.45

MPC

1.1

ClinPred

0.033

GERP RS

5.4

gMVP

0.71

Mutation Taster

=86/14

polymorphism

(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

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