rs34132052

Variant names:

• chr6-33304189-G-A
• rs34132052
• NM_003190.5:c.1239C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003190.5(TAPBP):​c.1239C>T​(p.Ser413Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,613,574 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (294 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (338 hom.)
• Consequence: TAPBP NM_003190.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.967
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-33304189-G-A is Benign according to our data. Variant chr6-33304189-G-A is described in ClinVar as Benign. ClinVar VariationId is 466396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.967 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	NM_003190.5	MANE Select	c.1239C>T	p.Ser413Ser	synonymous	Exon 6 of 8	NP_003181.3
	TAPBP	NM_172208.3		c.1239C>T	p.Ser413Ser	synonymous	Exon 6 of 7	NP_757345.2
	TAPBP	NM_001410875.1		c.1239C>T	p.Ser413Ser	synonymous	Exon 6 of 7	NP_001397804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.1239C>T	p.Ser413Ser	synonymous	Exon 6 of 8	ENSP00000395701.2
	TAPBP	ENST00000426633.6	TSL:1	c.1239C>T	p.Ser413Ser	synonymous	Exon 6 of 7	ENSP00000404833.2
	TAPBP	ENST00000489157.6	TSL:1	c.978C>T	p.Ser326Ser	synonymous	Exon 5 of 7	ENSP00000419659.1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4878 AN: 151674 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.0246

GnomAD2 exomes AF: 0.00869 AC: 2181 AN: 251040 AF XY: 0.00661

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00380 AC: 5557 AN: 1461782 Hom.: 338 Cov.: 32 AF XY: 0.00336 AC XY: 2442 AN XY: 727192

African (AFR) AF: 0.133 AC: 4457 AN: 33474

American (AMR) AF: 0.00539 AC: 241 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00125 AC: 108 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00867 AC: 50 AN: 5768

European-Non Finnish (NFE) AF: 0.000245 AC: 272 AN: 1111962

Other (OTH) AF: 0.00710 AC: 429 AN: 60394

GnomAD4 genome AF: 0.0322 AC: 4890 AN: 151792 Hom.: 294 Cov.: 31 AF XY: 0.0314 AC XY: 2332 AN XY: 74172

African (AFR) AF: 0.111 AC: 4606 AN: 41344

American (AMR) AF: 0.0129 AC: 196 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67950

Other (OTH) AF: 0.0244 AC: 51 AN: 2094

Alfa AF: 0.0133 Hom.: 58

Bravo AF: 0.0380

Asia WGS AF: 0.00577 AC: 21 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class I deficiency (1)
-	-	1	TAPBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.48
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34132052; hg19: chr6-33271966;