Variant 6-33304003-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000434618.7(TAPBP):c.1301-14A>G variant causes a splice polypyrimidine tract, 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
ENST00000434618.7 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-33304003-T-C is Benign according to our data. Variant chr6-33304003-T-C is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPBP	NM_003190.5 linkuse as main transcript	c.1301-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000434618.7	NP_003181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7 linkuse as main transcript	c.1301-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003190.5	ENSP00000395701	P2	O15533-1

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

GnomAD3 exomes

AF:

0.00336

AC:

844

AN:

251450

Hom.:

AF XY:

0.00278

AC XY:

378

AN XY:

135894

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 SAS exome

AF:

0.00167

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

Gnomad4 AFR exome

AF:

0.0277

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00167

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.00832

AC:

1260

AN:

151376

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

615

AN XY:

73972

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.00533

Gnomad4 ASJ

AF:

0.00376

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00168

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.00856

Alfa

AF:

0.00472

Hom.:

Bravo

AF:

0.00926

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.4

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over