7-154052934-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_130797.4(DPP6):c.114C>T(p.Gly38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,453,984 control chromosomes in the GnomAD database, including 16,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1172 hom., cov: 31)
  • Exomes 𝑓: 0.15 (14887 hom.)
• Consequence: DPP6 NM_130797.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.345

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 7-154052934-C-T is Benign according to our data. Variant chr7-154052934-C-T is described in ClinVar as [Benign]. Clinvar id is 1247688.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-154052934-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.345 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.114C>T	p.Gly38=	synonymous_variant	1/26	ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.114C>T	p.Gly38=	synonymous_variant	1/26	1	NM_130797.4
DPP6	ENST00000406326.5	c.114C>T	p.Gly38=	synonymous_variant	1/6	1
DPP6	ENST00000404039.5	c.51+165200C>T		intron_variant		1
DPP6	ENST00000706130.1	c.60+303926C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17451 AN: 148304 Hom.: 1173 Cov.: 31

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00275

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.131 AC: 14131 AN: 108040 Hom.: 1101 AF XY: 0.135 AC XY: 8112 AN XY: 59944

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.0697

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.00563

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.148 AC: 193698 AN: 1305578 Hom.: 14887 Cov.: 44 AF XY: 0.149 AC XY: 96273 AN XY: 644242

Gnomad4 AFR exome AF: 0.0492

Gnomad4 AMR exome AF: 0.0721

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.00323

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.118 AC: 17448 AN: 148406 Hom.: 1172 Cov.: 31 AF XY: 0.116 AC XY: 8427 AN XY: 72376

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.00276

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.123

Alfa AF: 0.137 Hom.: 328

Bravo AF: 0.110

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	11
Dann	Benign	0.96

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

Other links and lift over

dbSNP: rs554552970; hg19: chr7-153750019; COSMIC: COSV66710415; COSMIC: COSV66710415;