7-154052847-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_130797.4(DPP6):c.27T>C(p.Thr9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,535,464 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 0.00066 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00068 (0 hom.)
• Consequence: DPP6 NM_130797.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-154052847-T-C is Benign according to our data. Variant chr7-154052847-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BS2: High AC in GnomAd at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.27T>C	p.Thr9=	synonymous_variant	1/26	ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.27T>C	p.Thr9=	synonymous_variant	1/26	1	NM_130797.4
DPP6	ENST00000406326.5	c.27T>C	p.Thr9=	synonymous_variant	1/6	1
DPP6	ENST00000404039.5	c.51+165113T>C		intron_variant		1
DPP6	ENST00000706130.1	c.60+303839T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000661 AC: 100 AN: 151290 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000604

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000268 AC: 39 AN: 145540 Hom.: 0 AF XY: 0.000243 AC XY: 19 AN XY: 78262

Gnomad AFR exome AF: 0.000281

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000441

Gnomad FIN exome AF: 0.00100

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.000236

GnomAD4 exome AF: 0.000675 AC: 935 AN: 1384174 Hom.: 0 Cov.: 43 AF XY: 0.000649 AC XY: 443 AN XY: 682982

Gnomad4 AFR exome AF: 0.000225

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.00355

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000266

Gnomad4 FIN exome AF: 0.00146

Gnomad4 NFE exome AF: 0.000650

Gnomad4 OTH exome AF: 0.000906

GnomAD4 genome AF: 0.000661 AC: 100 AN: 151290 Hom.: 1 Cov.: 31 AF XY: 0.000758 AC XY: 56 AN XY: 73890

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00333

Gnomad4 NFE AF: 0.000604

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000727 Hom.: 0

Bravo AF: 0.000510

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

DPP6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.7
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs188616346; hg19: chr7-153749932;