7-153943389-C-T

Variant names:

• chr7-153943389-C-T
• rs10487687
• ENST00000404039.5:c.51+55655C>T

Variant summary

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

The NM_001364497.2(DPP6):​c.60+194381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,956 control chromosomes in the GnomAD database, including 10,970 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 0.37 (10970 hom., cov: 32)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 5 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
• 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

ENSG00000303399 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364497.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_001364497.2		c.60+194381C>T		intron	N/A	NP_001351426.1	A0A994J7K0
	DPP6	NM_001364498.2		c.60+194381C>T		intron	N/A	NP_001351427.1	A0A994J7K0
	DPP6	NM_001364499.2		c.60+194381C>T		intron	N/A	NP_001351428.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000404039.5	TSL:1	c.51+55655C>T		intron	N/A	ENSP00000385578.1	E9PF59
	DPP6	ENST00000706130.1		c.60+194381C>T		intron	N/A	ENSP00000516215.1	A0A994J7K0
	ENSG00000303399	ENST00000794146.1		n.98-225C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56767 AN: 151838 Hom.: 10963 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.374 AC: 56809 AN: 151956 Hom.: 10970 Cov.: 32 AF XY: 0.366 AC XY: 27150 AN XY: 74242

African (AFR) AF: 0.443 AC: 18332 AN: 41422

American (AMR) AF: 0.342 AC: 5229 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3468

East Asian (EAS) AF: 0.120 AC: 618 AN: 5154

South Asian (SAS) AF: 0.283 AC: 1357 AN: 4798

European-Finnish (FIN) AF: 0.316 AC: 3330 AN: 10554

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25584 AN: 67964

Other (OTH) AF: 0.370 AC: 781 AN: 2110

Alfa AF: 0.368 Hom.: 20086

Bravo AF: 0.374

Asia WGS AF: 0.216 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.67
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs10487687; hg19: chr7-153640474;