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6-33304144-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_003190.5(TAPBP):c.1284G>A(p.Lys428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,613,276 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00063 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

TAPBP
NM_003190.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0170
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 -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-33304144-C-T is Benign according to our data. Variant chr6-33304144-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 730560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.017 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAPBPNM_003190.5 linkuse as main transcriptc.1284G>A p.Lys428= synonymous_variant 6/8 ENST00000434618.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAPBPENST00000434618.7 linkuse as main transcriptc.1284G>A p.Lys428= synonymous_variant 6/81 NM_003190.5 P2O15533-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000634
AC:
96
AN:
151356
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00224
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
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:
0.0000147
Gnomad OTH
AF:
0.000481
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
251072
Hom.:
0
AF XY:
0.000169
AC XY:
23
AN XY:
135716
show subpopulations
Gnomad AFR exome
AF:
0.00271
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000451
AC:
66
AN:
1461802
Hom.:
0
Cov.:
31
AF XY:
0.0000454
AC XY:
33
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00164
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000634
AC:
96
AN:
151474
Hom.:
1
Cov.:
31
AF XY:
0.000649
AC XY:
48
AN XY:
73984
show subpopulations
Gnomad4 AFR
AF:
0.00223
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000476
Alfa
AF:
0.000403
Hom.:
0
Bravo
AF:
0.000676
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Benign/Likely 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 testingInvitaeJun 03, 2021- -
TAPBP-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 15, 2021This variant is classified as likely 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
-0.81
Cadd
Benign
1.2
Dann
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs148137345; hg19: chr6-33271921; COSMIC: COSV101444924; COSMIC: COSV101444924; API