NM_003190.5:c.1252C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003190.5(TAPBP):c.1252C>T(p.Leu418Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,658 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 19 hom., cov: 31)

Exomes 𝑓: 0.016 ( 250 hom. )

Consequence

TAPBP
NM_003190.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.98

Publications

4 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: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 6-33304176-G-A is Benign according to our data. Variant chr6-33304176-G-A is described in ClinVar as Benign. ClinVar VariationId is 466397.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.98 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0127 (1923/151850) while in subpopulation AMR AF = 0.0213 (324/15226). AF 95% confidence interval is 0.0194. There are 19 homozygotes in GnomAd4. There are 882 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBP	NM_003190.5 link	c.1252C>T	p.Leu418Leu	synonymous_variant	Exon 6 of 8	ENST00000434618.7	NP_003181.3	O15533-1A0A024RCT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7 link	c.1252C>T	p.Leu418Leu	synonymous_variant	Exon 6 of 8	1	NM_003190.5	ENSP00000395701.2		O15533-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1922

AN:

151732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00421

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.0124

AC:

3111

AN:

251128

AF XY:

0.0129

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00945

Gnomad EAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0164

AC:

23973

AN:

1461808

Hom.:

250

Cov.:

AF XY:

0.0163

AC XY:

11862

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00335

AC:

112

AN:

33480

American (AMR)

AF:

0.0148

AC:

662

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00918

AC:

240

AN:

26132

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.00918

AC:

792

AN:

86232

European-Finnish (FIN)

AF:

0.00217

AC:

116

AN:

53408

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0189

AC:

21069

AN:

1111974

Other (OTH)

AF:

0.0149

AC:

897

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1349

2698

4047

5396

6745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.0127

AC:

1923

AN:

151850

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

882

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.00420

AC:

174

AN:

41428

American (AMR)

AF:

0.0213

AC:

324

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

AN:

3472

East Asian (EAS)

AF:

0.00117

AC:

AN:

5130

South Asian (SAS)

AF:

0.00749

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00303

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0184

AC:

1250

AN:

67910

Other (OTH)

AF:

0.0186

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

166

249

332

415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0165

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0201

EpiControl

AF:

0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

TAPBP-related disorder

Benign:1

Jul 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.1

(source)

DANN

Benign

0.69

PhyloP100

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over