6-32832635-C-G

Variant names:

• chr6-32832635-C-G
• NM_001290043.2:c.1135G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290043.2(TAP2):​c.1135G>C​(p.Val379Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V379I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53

Genes affected

TAP2 (HGNC:44): (transporter 2, ATP binding cassette subfamily B member) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules. [provided by RefSeq, Feb 2014]

ENSG00000250264 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09054336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1135G>C	p.Val379Leu	missense_variant	Exon 6 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1135G>C	p.Val379Leu	missense_variant	Exon 6 of 12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1135G>C	p.Val379Leu	missense_variant	Exon 6 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1135G>C	p.Val379Leu	missense_variant	Exon 6 of 15	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460778 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 726706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	0.0010
DANN	Benign	0.69
DEOGEN2	Benign	0.15	.;.;.;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.60	T;.;.;.
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.091	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.66	.;N;.;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.12	N;N;.;N
REVEL	Uncertain	0.35
Sift	Benign	0.38	T;T;.;T
Sift4G	Benign	0.96	.;T;T;T
Polyphen		0.0030	.;.;.;B
Vest4		0.081, 0.079, 0.077
MutPred		0.72		Loss of MoRF binding (P = 0.1012);Loss of MoRF binding (P = 0.1012);Loss of MoRF binding (P = 0.1012);Loss of MoRF binding (P = 0.1012);
MVP		0.19
MPC		0.45
ClinPred		0.061	T
GERP RS		-9.9
Varity_R		0.027
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-32800412;