rs61739590

Variant names:

• chr6-33304535-C-T
• rs61739590
• NM_003190.5:c.972G>A

Variant summary

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

The ENST00000434618.7(TAPBP):​c.972G>A​(p.Gly324Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 1,612,228 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (244 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (180 hom.)
• Consequence: TAPBP ENST00000434618.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.778
• Publications: 3 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=-0.71).
• BP6: Variant 6-33304535-C-T is Benign according to our data. Variant chr6-33304535-C-T is described in ClinVar as Benign. ClinVar VariationId is 466400.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.778 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434618.7. 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.972G>A	p.Gly324Gly	synonymous	Exon 5 of 8	NP_003181.3
	TAPBP	NM_172208.3		c.972G>A	p.Gly324Gly	synonymous	Exon 5 of 7	NP_757345.2
	TAPBP	NM_001410875.1		c.972G>A	p.Gly324Gly	synonymous	Exon 5 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.972G>A	p.Gly324Gly	synonymous	Exon 5 of 8	ENSP00000395701.2
	TAPBP	ENST00000426633.6	TSL:1	c.972G>A	p.Gly324Gly	synonymous	Exon 5 of 7	ENSP00000404833.2
	TAPBP	ENST00000489157.6	TSL:1	c.711G>A	p.Gly237Gly	synonymous	Exon 4 of 7	ENSP00000419659.1

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4930 AN: 152110 Hom.: 244 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.00879 AC: 2154 AN: 245140 AF XY: 0.00700

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.00910

Gnomad ASJ exome AF: 0.00151

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.000827

Gnomad OTH exome AF: 0.00500

GnomAD4 exome AF: 0.00354 AC: 5164 AN: 1460000 Hom.: 180 Cov.: 32 AF XY: 0.00308 AC XY: 2236 AN XY: 726368

African (AFR) AF: 0.105 AC: 3524 AN: 33474

American (AMR) AF: 0.0103 AC: 462 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26122

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

South Asian (SAS) AF: 0.000545 AC: 47 AN: 86228

European-Finnish (FIN) AF: 0.0000386 AC: 2 AN: 51762

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5766

European-Non Finnish (NFE) AF: 0.000491 AC: 546 AN: 1111906

Other (OTH) AF: 0.00838 AC: 506 AN: 60374

GnomAD4 genome AF: 0.0324 AC: 4937 AN: 152228 Hom.: 244 Cov.: 31 AF XY: 0.0310 AC XY: 2306 AN XY: 74420

African (AFR) AF: 0.107 AC: 4448 AN: 41502

American (AMR) AF: 0.0243 AC: 372 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68014

Other (OTH) AF: 0.0284 AC: 60 AN: 2114

Alfa AF: 0.0111 Hom.: 42

Bravo AF: 0.0382

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00142

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.9
DANN	Benign	0.55
PhyloP100		-0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61739590; hg19: chr6-33272312;