7-153941163-C-T

Position:

• chr7-153941163-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_001039350.3	c.51+53429C>T		intron_variant			NP_001034439.1
DPP6	NM_001364497.2	c.60+192155C>T		intron_variant			NP_001351426.1
DPP6	NM_001364498.2	c.60+192155C>T		intron_variant			NP_001351427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000404039.5	c.51+53429C>T		intron_variant		1		ENSP00000385578
DPP6	ENST00000706130.1	c.60+192155C>T		intron_variant				ENSP00000516215

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

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.0910

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.0631

Gnomad4 FIN AF: 0.0645

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.140

Alfa AF: 0.113 Hom.: 2139

Bravo AF: 0.151

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6973850; hg19: chr7-153638248;