NM_130434.5:c.1489G>A

Variant names:

• chr15-65474256-C-T
• rs185464262
• NM_130434.5:c.1489G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_130434.5(DPP8):​c.1489G>A​(p.Ala497Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DPP8 NM_130434.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03988716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130434.5. 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
	DPP8	NM_130434.5	MANE Select	c.1489G>A	p.Ala497Thr	missense	Exon 12 of 20	NP_569118.1	Q6V1X1-3
	DPP8	NM_001320875.2		c.1537G>A	p.Ala513Thr	missense	Exon 13 of 21	NP_001307804.1	Q6V1X1-1
	DPP8	NM_197960.4		c.1537G>A	p.Ala513Thr	missense	Exon 13 of 21	NP_932064.1	Q6V1X1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP8	ENST00000300141.11	TSL:1 MANE Select	c.1489G>A	p.Ala497Thr	missense	Exon 12 of 20	ENSP00000300141.6	Q6V1X1-3
	DPP8	ENST00000321147.10	TSL:1	c.1537G>A	p.Ala513Thr	missense	Exon 13 of 20	ENSP00000318111.6	Q6V1X1-2
	DPP8	ENST00000558559.1	TSL:1	c.289-7033G>A		intron	N/A	ENSP00000452643.1	H0YK36

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251398 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460186 Hom.: 0 Cov.: 28 AF XY: 0.00000275 AC XY: 2 AN XY: 726554

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110556

Other (OTH) AF: 0.0000497 AC: 3 AN: 60330

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152300 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.000392 AC: 6 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L
PhyloP100		1.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.036
Sift	Benign	0.12	T
Sift4G	Benign	0.25	T
Polyphen		0.17	B
Vest4		0.094
MVP		0.068
MPC		0.34
ClinPred		0.34	T
GERP RS		3.3
Varity_R		0.10
gMVP		0.42
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs185464262; hg19: chr15-65766594;