7-154052668-C-T

Position:

• chr7-154052668-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130797.4(DPP6):​c.-153C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,219,902 control chromosomes in the GnomAD database, including 200,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (21948 hom., cov: 29)
  • Exomes 𝑓: 0.58 (178854 hom.)
• Consequence: DPP6 NM_130797.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.508

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 7-154052668-C-T is Benign according to our data. Variant chr7-154052668-C-T is described in ClinVar as [Benign]. Clinvar id is 1183923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4	c.-153C>T		5_prime_UTR_premature_start_codon_gain_variant	1/26	ENST00000377770.8	NP_570629.2
DPP6	NM_130797.4	c.-153C>T		5_prime_UTR_variant	1/26	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770	c.-153C>T		5_prime_UTR_premature_start_codon_gain_variant	1/26	1	NM_130797.4	ENSP00000367001.3
DPP6	ENST00000377770	c.-153C>T		5_prime_UTR_variant	1/26	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.536 AC: 80355 AN: 149894 Hom.: 21933 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.575 AC: 615211 AN: 1069926 Hom.: 178854 Cov.: 32 AF XY: 0.577 AC XY: 298030 AN XY: 516330

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.652

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.536 AC: 80413 AN: 149976 Hom.: 21948 Cov.: 29 AF XY: 0.543 AC XY: 39712 AN XY: 73082

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.522

Alfa AF: 0.547 Hom.: 2765

Bravo AF: 0.523

Asia WGS AF: 0.544 AC: 1886 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1974615; hg19: chr7-153749753;