rs1352118532

Variant names:

• chr15-65474258-A-G
• NM_130434.5:c.1487T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-65474258-A-G
• chr15-65474258-A-T

Variant summary

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

The NM_130434.5(DPP8):​c.1487T>C​(p.Ile496Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. I496K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPP8 NM_130434.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.00

Genes affected

DPP8 (HGNC:16490): (dipeptidyl peptidase 8) This gene encodes a member of the peptidase S9B family, a small family of dipeptidyl peptidases that are able to cleave peptide substrates at a prolyl bond. The encoded protein shares similarity with dipeptidyl peptidase IV in that it is ubiquitously expressed, and hydrolyzes the same substrates. These similarities suggest that, like dipeptidyl peptidase IV, this protein may play a role in T-cell activation and immune function. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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=0.15369123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP8	NM_130434.5	c.1487T>C	p.Ile496Thr	missense_variant	Exon 12 of 20	ENST00000300141.11	NP_569118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP8	ENST00000300141.11	c.1487T>C	p.Ile496Thr	missense_variant	Exon 12 of 20	1	NM_130434.5	ENSP00000300141.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460180 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-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	0.065
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.;.;.;T
Eigen	Benign	-0.043
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;D;D;D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;.;.;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.027	B;B;B;B;B
Vest4		0.15
MutPred		0.61		Gain of disorder (P = 0.0245);.;.;Gain of disorder (P = 0.0245);Gain of disorder (P = 0.0245);
MVP		0.043
MPC		0.20
ClinPred		0.63	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr15-65766596;