NM_130797.4:c.244-89114A>G

Variant names:

• chr7-154357100-A-G
• rs10269638
• NM_130797.4:c.244-89114A>G

Variant summary

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

The NM_130797.4(DPP6):​c.244-89114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,236 control chromosomes in the GnomAD database, including 1,995 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 0.10 (1995 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.244-89114A>G		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.244-89114A>G		intron_variant	Intron 1 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15233 AN: 152120 Hom.: 1992 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.100 AC: 15272 AN: 152236 Hom.: 1995 Cov.: 33 AF XY: 0.0979 AC XY: 7286 AN XY: 74438

African (AFR) AF: 0.303 AC: 12571 AN: 41500

American (AMR) AF: 0.0508 AC: 777 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5186

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4826

European-Finnish (FIN) AF: 0.0202 AC: 215 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1222 AN: 68020

Other (OTH) AF: 0.0904 AC: 191 AN: 2112

Alfa AF: 0.0758 Hom.: 194

Bravo AF: 0.113

Asia WGS AF: 0.0390 AC: 137 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.015
DANN	Benign	0.51
PhyloP100		-0.75

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: rs10269638; hg19: chr7-154054185;