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GeneBe

6-33304176-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003190.5(TAPBP):c.1252C>T(p.Leu418=) 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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.98
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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 id is 466397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAPBPNM_003190.5 linkuse as main transcriptc.1252C>T p.Leu418= synonymous_variant 6/8 ENST00000434618.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAPBPENST00000434618.7 linkuse as main transcriptc.1252C>T p.Leu418= synonymous_variant 6/81 NM_003190.5 P2O15533-1

Frequencies

GnomAD3 genomes
AF:
0.0127
AC:
1922
AN:
151732
Hom.:
19
Cov.:
31
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
GnomAD3 exomes
AF:
0.0124
AC:
3111
AN:
251128
Hom.:
34
AF XY:
0.0129
AC XY:
1749
AN XY:
135742
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 SAS exome
AF:
0.00857
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.:
32
AF XY:
0.0163
AC XY:
11862
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00335
Gnomad4 AMR exome
AF:
0.0148
Gnomad4 ASJ exome
AF:
0.00918
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.00918
Gnomad4 FIN exome
AF:
0.00217
Gnomad4 NFE exome
AF:
0.0189
Gnomad4 OTH exome
AF:
0.0149
GnomAD4 genome
AF:
0.0127
AC:
1923
AN:
151850
Hom.:
19
Cov.:
31
AF XY:
0.0119
AC XY:
882
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.00420
Gnomad4 AMR
AF:
0.0213
Gnomad4 ASJ
AF:
0.00979
Gnomad4 EAS
AF:
0.00117
Gnomad4 SAS
AF:
0.00749
Gnomad4 FIN
AF:
0.00303
Gnomad4 NFE
AF:
0.0184
Gnomad4 OTH
AF:
0.0186
Alfa
AF:
0.0166
Hom.:
15
Bravo
AF:
0.0145
Asia WGS
AF:
0.00577
AC:
20
AN:
3478
EpiCase
AF:
0.0201
EpiControl
AF:
0.0218

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

MHC class I deficiency Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
TAPBP-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 01, 2019This 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
Dann
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144706539; hg19: chr6-33271953; COSMIC: COSV70457436; COSMIC: COSV70457436; API