12-6453644-A-G

Position:

• chr12-6453644-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.

• 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]

TAPBPL (HGNC:):

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	Protein	UniProt
TAPBPL	NM_018009.5	c.493A>G	p.Thr165Ala	missense_variant	3/7	ENST00000266556.8	NP_060479.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPBPL	ENST00000266556.8	c.493A>G	p.Thr165Ala	missense_variant	3/7	1	NM_018009.5	ENSP00000266556.7

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
MutationAssessor	Benign	-1.4	.;N
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;