12-6453644-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018009.5(TAPBPL):c.493A>G(p.Thr165Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,613,272 control chromosomes in the GnomAD database, including 395,533 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T165I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.67 (34054 hom., cov: 32)
  • Exomes 𝑓: 0.70 (361479 hom.)
• Consequence: TAPBPL NM_018009.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

Genes affected

TAPBPL (HGNC:30683): (TAP binding protein like) Tapasin, or TAPBP (MIM 601962), is a member of the variable-constant Ig superfamily that links major histocompatibility complex (MHC) class I molecules to the transporter associated with antigen processing (TAP; see MIM 170260) in the endoplasmic reticulum (ER). The TAPBP gene is located near the MHC complex on chromosome 6p21.3. TAPBPL is a member of the Ig superfamily that is localized on chromosome 12p13.3, a region somewhat paralogous to the MHC.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.336663E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPBPL	NM_018009.5	c.493A>G	p.Thr165Ala	missense_variant	3/7	ENST00000266556.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPBPL	ENST00000266556.8	c.493A>G	p.Thr165Ala	missense_variant	3/7	1	NM_018009.5	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101216 AN: 151954 Hom.: 34029 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.623

GnomAD3 exomes AF: 0.682 AC: 170695 AN: 250440 Hom.: 58817 AF XY: 0.688 AC XY: 93193 AN XY: 135448

Gnomad AFR exome AF: 0.596

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.571

Gnomad EAS exome AF: 0.772

Gnomad SAS exome AF: 0.762

Gnomad FIN exome AF: 0.707

Gnomad NFE exome AF: 0.693

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.702 AC: 1025482 AN: 1461200 Hom.: 361479 Cov.: 67 AF XY: 0.703 AC XY: 511166 AN XY: 726890

Gnomad4 AFR exome AF: 0.585

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.706

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.666 AC: 101289 AN: 152072 Hom.: 34054 Cov.: 32 AF XY: 0.667 AC XY: 49577 AN XY: 74338

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.628

Alfa AF: 0.685 Hom.: 62752

Bravo AF: 0.651

TwinsUK AF: 0.700 AC: 2594

ALSPAC AF: 0.716 AC: 2758

ESP6500AA AF: 0.587 AC: 2585

ESP6500EA AF: 0.692 AC: 5954

ExAC AF: 0.682 AC: 82821

EpiCase AF: 0.678

EpiControl AF: 0.679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.60
Dann	Benign	0.25
DEOGEN2	Benign	0.0022	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.20	T;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.97	N;N
REVEL	Benign	0.029
Sift	Benign	0.87	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.0	.;B
Vest4		0.0070
MPC		0.17
ClinPred		0.00081	T
GERP RS		1.7
Varity_R		0.028
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs2532500; hg19: chr12-6562810; COSMIC: COSV56945960; COSMIC: COSV56945960;