dbSNP rs73741554: TAPBP:c.1301-14A>G (chr6-33304003-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP3BP6_ModerateBS1BS2

The NM_003190.5(TAPBP):c.1301-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,240 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 13 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 28 hom. )

Consequence

TAPBP
NM_003190.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

Publications

1 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 -9 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 6-33304003-T-C is Benign according to our data. Variant chr6-33304003-T-C is described in ClinVar as Benign. ClinVar VariationId is 1169190.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00832 (1260/151376) while in subpopulation AFR AF = 0.0248 (1023/41210). AF 95% confidence interval is 0.0236. There are 13 homozygotes in GnomAd4. There are 615 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 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	Effect	Exon Rank	Protein	UniProt
TAPBP	NM_003190.5	MANE Select	c.1301-14A>G	intron	N/A	NP_003181.3
TAPBP	NM_172208.3		c.1301-14A>G	intron	N/A	NP_757345.2	A0A0A0MSV9
TAPBP	NM_001410875.1		c.1300+125A>G	intron	N/A	NP_001397804.1	A0A8V8TQC5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.1301-14A>G	intron	N/A	ENSP00000395701.2	O15533-1
TAPBP	ENST00000426633.6	TSL:1	c.1301-14A>G	intron	N/A	ENSP00000404833.2	O15533-3
TAPBP	ENST00000489157.6	TSL:1	c.1040-14A>G	intron	N/A	ENSP00000419659.1	O15533-4

Frequencies

GnomAD3 genomes

AF:

0.00826

AC:

1249

AN:

151258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00534

Gnomad ASJ

AF:

0.00376

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00168

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00865

GnomAD2 exomes

AF:

0.00336

AC:

844

AN:

251450

AF XY:

0.00278

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00230

AC:

3367

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1602

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0277

AC:

929

AN:

33480

American (AMR)

AF:

0.00436

AC:

195

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00279

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00167

AC:

144

AN:

86256

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0265

AC:

153

AN:

5768

European-Non Finnish (NFE)

AF:

0.00145

AC:

1617

AN:

1111996

Other (OTH)

AF:

0.00411

AC:

248

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

202

403

605

806

1008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00832

AC:

1260

AN:

151376

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

615

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.0248

AC:

1023

AN:

41210

American (AMR)

AF:

0.00533

AC:

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.00376

AC:

AN:

3458

East Asian (EAS)

AF:

0.000195

AC:

AN:

5120

South Asian (SAS)

AF:

0.00168

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.000190

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

67818

Other (OTH)

AF:

0.00856

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00404

Hom.:

Bravo

AF:

0.00926

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance: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

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.4

(source)

DANN

Benign

0.86

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.55

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.45

Position offset: -1

DS_AL_spliceai

0.55

Position offset: -14

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

Publications

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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