Genetic Variant NM_018009.5:c.125C>T (chr12-6453127-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018009.5(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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4562 hom., cov: 31)

Exomes 𝑓: 0.28 ( 56905 hom. )

Consequence

TAPBPL
NM_018009.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

Publications

34 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAPBPL	NM_018009.5 link	c.125C>T	p.Ala42Val	missense_variant	Exon 2 of 7	ENST00000266556.8	NP_060479.3	Q9BX59-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBPL	ENST00000266556.8 link	c.125C>T	p.Ala42Val	missense_variant	Exon 2 of 7	1	NM_018009.5	ENSP00000266556.7		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

GnomAD2 exomes

AF:

0.261

AC:

54654

AN:

209442

AF XY:

0.269

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 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

African (AFR)

AF:

0.113

AC:

3786

AN:

33366

American (AMR)

AF:

0.153

AC:

6052

AN:

39684

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

7274

AN:

25518

East Asian (EAS)

AF:

0.341

AC:

13281

AN:

38928

South Asian (SAS)

AF:

0.303

AC:

25061

AN:

82578

European-Finnish (FIN)

AF:

0.291

AC:

15077

AN:

51764

Middle Eastern (MID)

AF:

0.272

AC:

1541

AN:

5668

European-Non Finnish (NFE)

AF:

0.284

AC:

312400

AN:

1099830

Other (OTH)

AF:

0.270

AC:

16047

AN:

59514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

17892

35784

53677

71569

89461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10366

20732

31098

41464

51830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.235

AC:

35675

AN:

151790

Hom.:

4562

Cov.:

AF XY:

0.236

AC XY:

17517

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.122

AC:

5065

AN:

41438

American (AMR)

AF:

0.210

AC:

3210

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

975

AN:

3468

East Asian (EAS)

AF:

0.324

AC:

1664

AN:

5134

South Asian (SAS)

AF:

0.311

AC:

1492

AN:

4804

European-Finnish (FIN)

AF:

0.296

AC:

3121

AN:

10532

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19215

AN:

67848

Other (OTH)

AF:

0.237

AC:

498

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1347

2693

4040

5386

6733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.272

Hom.:

18044

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

(source)

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

PhyloP100

0.24

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over