chr12-6460817-C-T

Variant names:

• chr12-6460817-C-T
• rs2243977
• NM_018009.5:c.1208-38C>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.1208-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,604,406 control chromosomes in the GnomAD database, including 68,157 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 (5025 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63132 hom.)
• Consequence: TAPBPL NM_018009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 22 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	NM_018009.5	MANE Select	c.1208-38C>T		intron	N/A	NP_060479.3
	TAPBPL	NM_001351355.2		c.818-38C>T		intron	N/A	NP_001338284.1
	TAPBPL	NR_147126.2		n.1280-38C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPBPL	ENST00000266556.8	TSL:1 MANE Select	c.1208-38C>T		intron	N/A	ENSP00000266556.7	Q9BX59-1
	TAPBPL	ENST00000853206.1		c.1208-38C>T		intron	N/A	ENSP00000523265.1
	TAPBPL	ENST00000954553.1		c.1208-38C>T		intron	N/A	ENSP00000624612.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36893 AN: 152006 Hom.: 5025 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: 0.332

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.248

GnomAD2 exomes AF: 0.273 AC: 68205 AN: 249896 AF XY: 0.284

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.281

GnomAD4 exome AF: 0.292 AC: 423452 AN: 1452282 Hom.: 63132 Cov.: 28 AF XY: 0.295 AC XY: 212994 AN XY: 723034

African (AFR) AF: 0.109 AC: 3632 AN: 33280

American (AMR) AF: 0.152 AC: 6791 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7479 AN: 26040

East Asian (EAS) AF: 0.345 AC: 13667 AN: 39612

South Asian (SAS) AF: 0.342 AC: 29447 AN: 86010

European-Finnish (FIN) AF: 0.294 AC: 15678 AN: 53250

Middle Eastern (MID) AF: 0.319 AC: 1831 AN: 5744

European-Non Finnish (NFE) AF: 0.297 AC: 327868 AN: 1103674

Other (OTH) AF: 0.284 AC: 17059 AN: 60028

GnomAD4 genome AF: 0.243 AC: 36902 AN: 152124 Hom.: 5025 Cov.: 32 AF XY: 0.244 AC XY: 18148 AN XY: 74374

African (AFR) AF: 0.117 AC: 4854 AN: 41516

American (AMR) AF: 0.222 AC: 3392 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1715 AN: 5176

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3185 AN: 10572

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20073 AN: 67962

Other (OTH) AF: 0.251 AC: 530 AN: 2112

Alfa AF: 0.257 Hom.: 2558

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	-0.83
CADD	Benign	4.1
DANN	Benign	0.48
PhyloP100		0.0010
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: rs2243977; hg19: chr12-6569983; COSMIC: COSV107244308; COSMIC: COSV107244308;