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GeneBe

7-154052919-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_130797.4(DPP6):c.99C>G(p.Pro33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,496,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00045 ( 1 hom. )

Consequence

DPP6
NM_130797.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-154052919-C-G is Benign according to our data. Variant chr7-154052919-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658247.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.19 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 68 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DPP6NM_130797.4 linkuse as main transcriptc.99C>G p.Pro33= synonymous_variant 1/26 ENST00000377770.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPP6ENST00000377770.8 linkuse as main transcriptc.99C>G p.Pro33= synonymous_variant 1/261 NM_130797.4 P42658-1
DPP6ENST00000406326.5 linkuse as main transcriptc.99C>G p.Pro33= synonymous_variant 1/61
DPP6ENST00000404039.5 linkuse as main transcriptc.51+165185C>G intron_variant 1
DPP6ENST00000706130.1 linkuse as main transcriptc.60+303911C>G intron_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000454
AC:
68
AN:
149632
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000267
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000419
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000743
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000446
AC:
55
AN:
123186
Hom.:
0
AF XY:
0.000488
AC XY:
33
AN XY:
67588
show subpopulations
Gnomad AFR exome
AF:
0.000232
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000923
Gnomad FIN exome
AF:
0.000389
Gnomad NFE exome
AF:
0.000913
Gnomad OTH exome
AF:
0.000545
GnomAD4 exome
AF:
0.000446
AC:
601
AN:
1346944
Hom.:
1
Cov.:
44
AF XY:
0.000463
AC XY:
308
AN XY:
664774
show subpopulations
Gnomad4 AFR exome
AF:
0.0000346
Gnomad4 AMR exome
AF:
0.000265
Gnomad4 ASJ exome
AF:
0.0000423
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000256
Gnomad4 FIN exome
AF:
0.000340
Gnomad4 NFE exome
AF:
0.000522
Gnomad4 OTH exome
AF:
0.000434
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000454
AC:
68
AN:
149736
Hom.:
0
Cov.:
31
AF XY:
0.000328
AC XY:
24
AN XY:
73120
show subpopulations
Gnomad4 AFR
AF:
0.000243
Gnomad4 AMR
AF:
0.000266
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000419
Gnomad4 NFE
AF:
0.000743
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000467
Hom.:
0
Bravo
AF:
0.000544

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2023DPP6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
Cadd
Benign
10
Dann
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs528815814; hg19: chr7-153750004; API