rs2071888

Variant names:

• chr6-33305078-G-C
• rs2071888
• NM_003190.5:c.779C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-33305078-G-C
• chr6-33305078-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003190.5(TAPBP):​c.779C>G​(p.Thr260Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,886 control chromosomes in the GnomAD database, including 241,705 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T260G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.59 (27444 hom., cov: 31)
  • Exomes 𝑓: 0.54 (214261 hom.)
• Consequence: TAPBP NM_003190.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 0.365
• Publications: 59 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet
• MHC class I deficiency 1

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.641656E-6).
• BP6: Variant 6-33305078-G-C is Benign according to our data. Variant chr6-33305078-G-C is described in ClinVar as Benign. ClinVar VariationId is 403518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	NM_003190.5	MANE Select	c.779C>G	p.Thr260Arg	missense	Exon 4 of 8	NP_003181.3
	TAPBP	NM_172208.3		c.779C>G	p.Thr260Arg	missense	Exon 4 of 7	NP_757345.2	A0A0A0MSV9
	TAPBP	NM_001410875.1		c.779C>G	p.Thr260Arg	missense	Exon 4 of 7	NP_001397804.1	A0A8V8TQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBP	ENST00000434618.7	TSL:1 MANE Select	c.779C>G	p.Thr260Arg	missense	Exon 4 of 8	ENSP00000395701.2	O15533-1
	TAPBP	ENST00000426633.6	TSL:1	c.779C>G	p.Thr260Arg	missense	Exon 4 of 7	ENSP00000404833.2	O15533-3
	TAPBP	ENST00000489157.6	TSL:1	c.518C>G	p.Thr173Arg	missense	Exon 3 of 7	ENSP00000419659.1	O15533-4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90039 AN: 151882 Hom.: 27396 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.585

GnomAD2 exomes AF: 0.559 AC: 140530 AN: 251460 AF XY: 0.563

Gnomad AFR exome AF: 0.749

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.379

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.567

GnomAD4 exome AF: 0.538 AC: 786499 AN: 1461886 Hom.: 214261 Cov.: 84 AF XY: 0.542 AC XY: 394195 AN XY: 727242

African (AFR) AF: 0.746 AC: 24963 AN: 33480

American (AMR) AF: 0.547 AC: 24474 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 14924 AN: 26136

East Asian (EAS) AF: 0.375 AC: 14901 AN: 39700

South Asian (SAS) AF: 0.654 AC: 56371 AN: 86258

European-Finnish (FIN) AF: 0.529 AC: 28234 AN: 53420

Middle Eastern (MID) AF: 0.579 AC: 3341 AN: 5768

European-Non Finnish (NFE) AF: 0.527 AC: 585603 AN: 1112008

Other (OTH) AF: 0.558 AC: 33688 AN: 60394

GnomAD4 genome AF: 0.593 AC: 90140 AN: 152000 Hom.: 27444 Cov.: 31 AF XY: 0.593 AC XY: 44066 AN XY: 74280

African (AFR) AF: 0.736 AC: 30516 AN: 41464

American (AMR) AF: 0.578 AC: 8828 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2090 AN: 5146

South Asian (SAS) AF: 0.650 AC: 3137 AN: 4824

European-Finnish (FIN) AF: 0.527 AC: 5566 AN: 10556

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36250 AN: 67952

Other (OTH) AF: 0.583 AC: 1228 AN: 2106

Alfa AF: 0.552 Hom.: 7526

Bravo AF: 0.601

TwinsUK AF: 0.518 AC: 1922

ALSPAC AF: 0.526 AC: 2026

ESP6500AA AF: 0.736 AC: 3241

ESP6500EA AF: 0.542 AC: 4662

ExAC AF: 0.568 AC: 68959

Asia WGS AF: 0.526 AC: 1831 AN: 3478

EpiCase AF: 0.549

EpiControl AF: 0.543

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	MHC class I deficiency (3)
-	-	1	not specified (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.18
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.027	T
MetaRNN	Benign	0.0000046	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.36
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.069
MPC		0.39
ClinPred		0.00071	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.29
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2071888; hg19: chr6-33272855; COSMIC: COSV70457054; COSMIC: COSV70457054;