Variant 7-154052947-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_130797.4(DPP6):c.127C>G(p.Pro43Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,088,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DPP6
NM_130797.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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:

DPP6 (HGNC:):

DPP6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.103254825).

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4 linkuse as main transcript	c.127C>G	p.Pro43Ala	missense_variant	1/26	ENST00000377770.8	NP_570629.2	P42658-1Q8IYG9A7E2E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DPP6	ENST00000377770.8 linkuse as main transcript	c.127C>G	p.Pro43Ala	missense_variant	1/26	1	NM_130797.4	ENSP00000367001.3	P42658-1
DPP6	ENST00000406326.5 linkuse as main transcript	c.127C>G	p.Pro43Ala	missense_variant	1/6	1		ENSP00000384393.1	Q8IYG9
DPP6	ENST00000404039.5 linkuse as main transcript	c.51+165213C>G		intron_variant		1		ENSP00000385578.1	E9PF59
DPP6	ENST00000706130.1 linkuse as main transcript	c.60+303939C>G		intron_variant				ENSP00000516215.1	A0A994J7K0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000193

AC:

AN:

51846

Hom.:

AF XY:

0.00

AC XY:

AN XY:

30932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000420

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1088254

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

525706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000452

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:

0.0000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.074

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.046

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.027

D;T

Polyphen

0.93

P;B

Vest4

0.091

MutPred

0.18

Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);

MVP

0.043

MPC

0.40

ClinPred

0.43

GERP RS

0.52

Varity_R

0.038

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over