7-154052934-C-T

Variant names:

• chr7-154052934-C-T
• rs554552970
• NM_130797.4:c.114C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_130797.4(DPP6):​c.114C>T​(p.Gly38Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,453,984 control chromosomes in the GnomAD database, including 16,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1172 hom., cov: 31)
  • Exomes 𝑓: 0.15 (14887 hom.)
• Consequence: DPP6 NM_130797.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.345
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 7-154052934-C-T is Benign according to our data. Variant chr7-154052934-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.345 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 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.114C>T	p.Gly38Gly	synonymous	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.114C>T	p.Gly38Gly	synonymous	Exon 1 of 6	NP_001277182.1	Q8IYG9
	DPP6	NM_001364497.2		c.60+303926C>T		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.114C>T	p.Gly38Gly	synonymous	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.114C>T	p.Gly38Gly	synonymous	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000404039.5	TSL:1	c.51+165200C>T		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17451 AN: 148304 Hom.: 1173 Cov.: 31

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00275

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.131 AC: 14131 AN: 108040 AF XY: 0.135

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.0697

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.00563

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.148 AC: 193698 AN: 1305578 Hom.: 14887 Cov.: 44 AF XY: 0.149 AC XY: 96273 AN XY: 644242

African (AFR) AF: 0.0492 AC: 1340 AN: 27248

American (AMR) AF: 0.0721 AC: 2314 AN: 32114

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3113 AN: 22168

East Asian (EAS) AF: 0.00323 AC: 92 AN: 28482

South Asian (SAS) AF: 0.161 AC: 12269 AN: 76258

European-Finnish (FIN) AF: 0.130 AC: 4065 AN: 31188

Middle Eastern (MID) AF: 0.157 AC: 655 AN: 4178

European-Non Finnish (NFE) AF: 0.158 AC: 162898 AN: 1031224

Other (OTH) AF: 0.132 AC: 6952 AN: 52718

GnomAD4 genome AF: 0.118 AC: 17448 AN: 148406 Hom.: 1172 Cov.: 31 AF XY: 0.116 AC XY: 8427 AN XY: 72376

African (AFR) AF: 0.0542 AC: 2230 AN: 41126

American (AMR) AF: 0.104 AC: 1547 AN: 14932

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 543 AN: 3414

East Asian (EAS) AF: 0.00276 AC: 14 AN: 5074

South Asian (SAS) AF: 0.153 AC: 737 AN: 4812

European-Finnish (FIN) AF: 0.141 AC: 1280 AN: 9068

Middle Eastern (MID) AF: 0.197 AC: 57 AN: 290

European-Non Finnish (NFE) AF: 0.160 AC: 10649 AN: 66726

Other (OTH) AF: 0.123 AC: 253 AN: 2052

Alfa AF: 0.137 Hom.: 328

Bravo AF: 0.110

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		-0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs554552970; hg19: chr7-153750019; COSMIC: COSV66710415; COSMIC: COSV66710415;