7-153941163-C-T

Variant names:

• chr7-153941163-C-T
• rs6973850
• ENST00000404039.5:c.51+53429C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000404039.5(DPP6):​c.51+53429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,228 control chromosomes in the GnomAD database, including 1,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1789 hom., cov: 33)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 7 publications found

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
• intellectual disability, autosomal dominant 33

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404039.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_001364497.2		c.60+192155C>T		intron	N/A	NP_001351426.1
	DPP6	NM_001364498.2		c.60+192155C>T		intron	N/A	NP_001351427.1
	DPP6	NM_001364499.2		c.60+192155C>T		intron	N/A	NP_001351428.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000404039.5	TSL:1	c.51+53429C>T		intron	N/A	ENSP00000385578.1
	DPP6	ENST00000706130.1		c.60+192155C>T		intron	N/A	ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21727 AN: 152110 Hom.: 1786 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.143 AC: 21753 AN: 152228 Hom.: 1789 Cov.: 33 AF XY: 0.139 AC XY: 10364 AN XY: 74436

African (AFR) AF: 0.224 AC: 9283 AN: 41514

American (AMR) AF: 0.157 AC: 2401 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 316 AN: 3472

East Asian (EAS) AF: 0.0425 AC: 220 AN: 5176

South Asian (SAS) AF: 0.0631 AC: 305 AN: 4830

European-Finnish (FIN) AF: 0.0645 AC: 684 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8026 AN: 68032

Other (OTH) AF: 0.140 AC: 296 AN: 2116

Alfa AF: 0.120 Hom.: 5055

Bravo AF: 0.151

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6973850; hg19: chr7-153638248;