dbSNP rs572667303: DPP6:p.Asp76Ala (chr7-154053047-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130797.4(DPP6):c.227A>C(p.Asp76Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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. D76N) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DPP6
NM_130797.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

DPP6 (HGNC:3010): (dipeptidyl peptidase like 6) This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

DPP6 links:

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ACMG classification

Classification made for transcript

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=0.10449326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4 link	c.227A>C	p.Asp76Ala	missense_variant	Exon 1 of 26	ENST00000377770.8	NP_570629.2	P42658-1Q8IYG9A7E2E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DPP6	ENST00000377770.8 link	c.227A>C	p.Asp76Ala	missense_variant	Exon 1 of 26	1	NM_130797.4	ENSP00000367001.3	P42658-1
DPP6	ENST00000406326.5 link	c.227A>C	p.Asp76Ala	missense_variant	Exon 1 of 6	1		ENSP00000384393.1	Q8IYG9
DPP6	ENST00000404039.5 link	c.51+165313A>C		intron_variant	Intron 1 of 25	1		ENSP00000385578.1	E9PF59
DPP6	ENST00000706130.1 link	c.60+304039A>C		intron_variant	Intron 2 of 26			ENSP00000516215.1	A0A994J7K0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

903700

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

421806

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.11

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.098

Sift

Uncertain

0.029

D;T

Sift4G

Benign

0.38

T;T

Polyphen

0.12

B;B

Vest4

0.12

MutPred

0.19

Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);

MVP

0.13

MPC

0.52

ClinPred

0.81

GERP RS

2.0

Varity_R

0.15

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over