NM_130797.4:c.244-176019G>A

Variant names:

• chr7-154270195-G-A
• rs10274025
• NM_130797.4:c.244-176019G>A

Variant summary

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

The NM_130797.4(DPP6):​c.244-176019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,076 control chromosomes in the GnomAD database, including 2,125 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 (2125 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.244-176019G>A		intron_variant	Intron 1 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.244-176019G>A		intron_variant	Intron 1 of 25	1	NM_130797.4	ENSP00000367001.3
DPP6	ENST00000404039.5	c.52-176019G>A		intron_variant	Intron 1 of 25	1		ENSP00000385578.1
DPP6	ENST00000406326.5	c.244-176019G>A		intron_variant	Intron 1 of 5	1		ENSP00000384393.1
DPP6	ENST00000706130.1	c.61-176019G>A		intron_variant	Intron 2 of 26			ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21815 AN: 151958 Hom.: 2121 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0452

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.144 AC: 21836 AN: 152076 Hom.: 2125 Cov.: 32 AF XY: 0.141 AC XY: 10489 AN XY: 74334

African (AFR) AF: 0.276 AC: 11452 AN: 41440

American (AMR) AF: 0.124 AC: 1892 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3472

East Asian (EAS) AF: 0.0575 AC: 297 AN: 5166

South Asian (SAS) AF: 0.137 AC: 661 AN: 4828

European-Finnish (FIN) AF: 0.0474 AC: 501 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6223 AN: 68008

Other (OTH) AF: 0.160 AC: 336 AN: 2104

Alfa AF: 0.113 Hom.: 1936

Bravo AF: 0.158

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		-0.089

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: rs10274025; hg19: chr7-153967280; COSMIC: COSV66742896;