rs2244083

Variant names:

• chr12-6461373-A-T
• rs2244083
• NM_018009.5:c.1291+435A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	NM_018009.5	MANE Select	c.1291+435A>T		intron	N/A	NP_060479.3
	TAPBPL	NR_147126.2		n.1578A>T		non_coding_transcript_exon	Exon 7 of 8
	TAPBPL	NR_147127.2		n.1588A>T		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	ENST00000266556.8	TSL:1 MANE Select	c.1291+435A>T		intron	N/A	ENSP00000266556.7
	TAPBPL	ENST00000544289.1	TSL:2	n.339A>T		non_coding_transcript_exon	Exon 1 of 2
	TAPBPL	ENST00000539384.5	TSL:5	n.1322+435A>T		intron	N/A

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

African (AFR) AF: 0.106 AC: 1743 AN: 16428

American (AMR) AF: 0.194 AC: 747 AN: 3846

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 1563 AN: 5542

East Asian (EAS) AF: 0.345 AC: 1681 AN: 4870

South Asian (SAS) AF: 0.337 AC: 7396 AN: 21962

European-Finnish (FIN) AF: 0.268 AC: 264 AN: 984

Middle Eastern (MID) AF: 0.330 AC: 553 AN: 1676

European-Non Finnish (NFE) AF: 0.296 AC: 229598 AN: 775850

Other (OTH) AF: 0.288 AC: 8208 AN: 28492

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

African (AFR) AF: 0.117 AC: 4844 AN: 41508

American (AMR) AF: 0.222 AC: 3385 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3464

East Asian (EAS) AF: 0.331 AC: 1702 AN: 5148

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4822

European-Finnish (FIN) AF: 0.299 AC: 3157 AN: 10548

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20072 AN: 67958

Other (OTH) AF: 0.252 AC: 533 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2244083; hg19: chr12-6570539;