7-154052934-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_130797.4(DPP6):​c.114C>A​(p.Gly38Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G38G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 NM_130797.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.345 with no splicing effect.

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>A	p.Gly38Gly	synonymous	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.114C>A	p.Gly38Gly	synonymous	Exon 1 of 6	NP_001277182.1	Q8IYG9
	DPP6	NM_001364497.2		c.60+303926C>A		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>A	p.Gly38Gly	synonymous	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.114C>A	p.Gly38Gly	synonymous	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000404039.5	TSL:1	c.51+165200C>A		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000926 AC: 1 AN: 108040 AF XY: 0.0000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1306056 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 644492

African (AFR) AF: 0.00 AC: 0 AN: 27248

American (AMR) AF: 0.00 AC: 0 AN: 32124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22178

East Asian (EAS) AF: 0.00 AC: 0 AN: 28482

South Asian (SAS) AF: 0.00 AC: 0 AN: 76280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1031548

Other (OTH) AF: 0.00 AC: 0 AN: 52748

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		-0.34

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: rs554552970; hg19: chr7-153750019;