rs2244083

Positions:

• chr12-6461373-A-T

Variant summary

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

The NM_018009.5(TAPBPL):​c.1291+435A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,011,684 control chromosomes in the GnomAD database, including 42,309 homozygotes. In-silico tool predicts 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 (5008 hom., cov: 32)
  • Exomes 𝑓: 0.29 (37301 hom.)
• Consequence: TAPBPL NM_018009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPBPL	NM_018009.5	c.1291+435A>T		intron_variant		ENST00000266556.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPBPL	ENST00000266556.8	c.1291+435A>T		intron_variant		1	NM_018009.5	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36828 AN: 151914 Hom.: 5008 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.293 AC: 251753 AN: 859650 Hom.: 37301 Cov.: 32 AF XY: 0.294 AC XY: 117413 AN XY: 399666

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.242 AC: 36838 AN: 152034 Hom.: 5008 Cov.: 32 AF XY: 0.243 AC XY: 18086 AN XY: 74284

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.252

Alfa AF: 0.251 Hom.: 683

Bravo AF: 0.227

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.56

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: rs2244083; hg19: chr12-6570539;