rs561629511

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_003190.5(TAPBP):c.562A>T(p.Thr188Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000857 in 1,575,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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. T188I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

TAPBP
NM_003190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.145

Publications

0 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

TAPBP links:

Genome browser will be placed here

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=0.02966243).

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
TAPBP	NM_003190.5	MANE Select	c.562A>T	p.Thr188Ser	missense	Exon 4 of 8	NP_003181.3
TAPBP	NM_172208.3		c.562A>T	p.Thr188Ser	missense	Exon 4 of 7	NP_757345.2
TAPBP	NM_001410875.1		c.562A>T	p.Thr188Ser	missense	Exon 4 of 7	NP_001397804.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.562A>T	p.Thr188Ser	missense	Exon 4 of 8	ENSP00000395701.2
TAPBP	ENST00000426633.6	TSL:1	c.562A>T	p.Thr188Ser	missense	Exon 4 of 7	ENSP00000404833.2
TAPBP	ENST00000489157.6	TSL:1	c.301A>T	p.Thr101Ser	missense	Exon 3 of 7	ENSP00000419659.1

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000974

AC:

AN:

215678

AF XY:

0.0000866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000611

Gnomad OTH exome

AF:

0.000194

GnomAD4 exome

AF:

0.0000912

AC:

130

AN:

1425292

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

705360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32440

American (AMR)

AF:

0.00

AC:

AN:

40714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23212

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39484

South Asian (SAS)

AF:

0.000527

AC:

AN:

79664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51616

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.0000713

AC:

AN:

1093798

Other (OTH)

AF:

0.000136

AC:

AN:

58802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000332

AC:

AN:

150404

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73306

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40688

American (AMR)

AF:

0.00

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000591

AC:

AN:

67674

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000825

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class I deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.8

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.55

M_CAP

Benign

0.0065

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.98

PhyloP100

0.14

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.21

REVEL

Benign

0.041

Sift

Benign

0.59

Sift4G

Benign

0.13

Polyphen

0.040

Vest4

0.095

MutPred

0.28

Gain of disorder (P = 0.0399)

MVP

0.30

MPC

0.31

ClinPred

0.015

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

gMVP

0.12

Mutation Taster

=83/17

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over