Variant chr12-6453127-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000266556.8(TAPBPL):c.125C>T(p.Ala42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,588,640 control chromosomes in the GnomAD database, including 61,467 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 0.24 ( 4562 hom., cov: 31)

Exomes 𝑓: 0.28 ( 56905 hom. )

Consequence

TAPBPL
ENST00000266556.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015131831).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPBPL	NM_018009.5 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant	2/7	ENST00000266556.8	NP_060479.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPBPL	ENST00000266556.8 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant	2/7	1	NM_018009.5	ENSP00000266556	P1	Q9BX59-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35659

AN:

151670

Hom.:

4563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.379

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.261

AC:

54654

AN:

209442

Hom.:

7530

AF XY:

0.269

AC XY:

30201

AN XY:

112112

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.279

AC:

400519

AN:

1436850

Hom.:

56905

Cov.:

AF XY:

0.280

AC XY:

199643

AN XY:

712214

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.235

AC:

35675

AN:

151790

Hom.:

4562

Cov.:

AF XY:

0.236

AC XY:

17517

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.274

Hom.:

13680

Bravo

AF:

0.222

TwinsUK

AF:

0.271

AC:

1006

ALSPAC

AF:

0.284

AC:

1093

ESP6500AA

AF:

0.121

AC:

535

ESP6500EA

AF:

0.288

AC:

2476

ExAC

AF:

0.236

AC:

28322

Asia WGS

AF:

0.235

AC:

818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

DANN

Benign

0.71

DEOGEN2

Benign

0.0020

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

1.8

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.015

MPC

0.18

ClinPred

0.0068

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over