chr12-6453127-C-T

Variant names:

• chr12-6453127-C-T
• rs2041385
• NM_018009.5:c.125C>T

Variant summary

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

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. 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4562 hom., cov: 31)
  • Exomes 𝑓: 0.28 (56905 hom.)
• Consequence: TAPBPL NM_018009.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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=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	c.125C>T	p.Ala42Val	missense_variant	Exon 2 of 7	ENST00000266556.8	NP_060479.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35659 AN: 151670 Hom.: 4563 Cov.: 31

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

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.: 51 AF XY: 0.280 AC XY: 199643 AN XY: 712214

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.: 31 AF XY: 0.236 AC XY: 17517 AN XY: 74142

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	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.8
DANN	Benign	0.71
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.015
MPC		0.18
ClinPred		0.0068	T
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

Other links and lift over

dbSNP: rs2041385; hg19: chr12-6562293; COSMIC: COSV56947458; COSMIC: COSV56947458;