rs1225695566

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_130797.4(DPP6):c.140G>T(p.Arg47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,136,718 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. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. R47R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

DPP6
NM_130797.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.138

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant primary microcephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
paroxysmal familial ventricular fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ventricular fibrillation, paroxysmal familial, 2
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability, autosomal dominant 33
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

DPP6 links:

ENSG00000203335 (HGNC:):

ENSG00000203335 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043008655).

BP6

Variant 7-154052960-G-T is Benign according to our data. Variant chr7-154052960-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1297601.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 7 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP6	NM_130797.4	MANE Select	c.140G>T	p.Arg47Leu	missense	Exon 1 of 26	NP_570629.2	P42658-1
DPP6	NM_001290253.2		c.140G>T	p.Arg47Leu	missense	Exon 1 of 6	NP_001277182.1	Q8IYG9
DPP6	NM_001364497.2		c.60+303952G>T		intron	N/A	NP_001351426.1	A0A994J7K0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP6	ENST00000377770.8	TSL:1 MANE Select	c.140G>T	p.Arg47Leu	missense	Exon 1 of 26	ENSP00000367001.3	P42658-1
DPP6	ENST00000406326.5	TSL:1	c.140G>T	p.Arg47Leu	missense	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
DPP6	ENST00000404039.5	TSL:1	c.51+165226G>T		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes

AF:

0.0000476

AC:

AN:

147172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000106

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000233

AC:

AN:

25702

AF XY:

0.000304

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

161

AN:

989546

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

AN XY:

470728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19316

American (AMR)

AF:

0.00

AC:

AN:

6146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11560

East Asian (EAS)

AF:

0.0000655

AC:

AN:

15264

South Asian (SAS)

AF:

0.00

AC:

AN:

26808

European-Finnish (FIN)

AF:

0.0000697

AC:

AN:

14346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2414

European-Non Finnish (NFE)

AF:

0.000183

AC:

157

AN:

857770

Other (OTH)

AF:

0.0000557

AC:

AN:

35922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000476

AC:

AN:

147172

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

71602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40872

American (AMR)

AF:

0.00

AC:

AN:

14814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000106

AC:

AN:

66272

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.018

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

M_CAP

Benign

0.041

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

PhyloP100

0.14

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.53

REVEL

Benign

0.018

Sift

Benign

0.048

Sift4G

Uncertain

0.015

Polyphen

0.10

Vest4

0.063

MVP

0.043

MPC

0.51

ClinPred

0.035

GERP RS

-3.4

Varity_R

0.055

gMVP

0.28

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over