7-154052720-CT-C

Variant names:

• chr7-154052720-CT-C
• rs571183490
• NM_130797.4:c.-88delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_130797.4(DPP6):​c.-88delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4372 hom., cov: 6)
  • Exomes 𝑓: 0.40 (3673 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 NM_130797.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0930
• Publications: 2 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

ENSG00000203335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-154052720-CT-C is Benign according to our data. Variant chr7-154052720-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1259138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. 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_130797.4	MANE Select	c.-88delT		5_prime_UTR	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.-88delT		5_prime_UTR	Exon 1 of 6	NP_001277182.1	Q8IYG9
	DPP6	NM_001364497.2		c.60+303725delT		intron	N/A	NP_001351426.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.-88delT		5_prime_UTR	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.-88delT		5_prime_UTR	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000404039.5	TSL:1	c.51+164999delT		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.246 AC: 34774 AN: 141356 Hom.: 4379 Cov.: 6

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.237

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.400 AC: 300267 AN: 750086 Hom.: 3673 Cov.: 0 AF XY: 0.398 AC XY: 146689 AN XY: 368268

African (AFR) AF: 0.433 AC: 5751 AN: 13294

American (AMR) AF: 0.367 AC: 4993 AN: 13594

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 3196 AN: 9414

East Asian (EAS) AF: 0.429 AC: 4161 AN: 9702

South Asian (SAS) AF: 0.388 AC: 19219 AN: 49496

European-Finnish (FIN) AF: 0.316 AC: 3366 AN: 10642

Middle Eastern (MID) AF: 0.327 AC: 697 AN: 2132

European-Non Finnish (NFE) AF: 0.404 AC: 248306 AN: 614868

Other (OTH) AF: 0.393 AC: 10578 AN: 26944

GnomAD4 genome AF: 0.246 AC: 34759 AN: 141346 Hom.: 4372 Cov.: 6 AF XY: 0.247 AC XY: 16887 AN XY: 68326

African (AFR) AF: 0.253 AC: 9812 AN: 38712

American (AMR) AF: 0.266 AC: 3816 AN: 14340

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 613 AN: 3366

East Asian (EAS) AF: 0.385 AC: 1787 AN: 4646

South Asian (SAS) AF: 0.282 AC: 1246 AN: 4420

European-Finnish (FIN) AF: 0.183 AC: 1429 AN: 7820

Middle Eastern (MID) AF: 0.246 AC: 65 AN: 264

European-Non Finnish (NFE) AF: 0.236 AC: 15348 AN: 64932

Other (OTH) AF: 0.234 AC: 459 AN: 1958

Alfa AF: 0.0563 Hom.: 121

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs571183490; hg19: chr7-153749805;