rs571183490

Variant names:

• chr7-154052720-CTTTTT-C
• rs571183490
• NM_130797.4:c.-92_-88delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr7-154052720-CTTTTT-C
• chr7-154052720-CTTTTT-CTT
• chr7-154052720-CTTTTT-CTTT
• chr7-154052720-CTTTTT-CTTTT
• chr7-154052720-CTTTTT-CTTTTTT
• chr7-154052720-CTTTTT-CTTTTTTT
• chr7-154052720-CTTTTT-CTTTTTTTT
• chr7-154052720-CTTTTT-CTTTTTTTTT
• chr7-154052720-CTTTTT-CTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_130797.4(DPP6):​c.-92_-88delTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 NM_130797.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

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.-92_-88delTTTTT		5_prime_UTR	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.-92_-88delTTTTT		5_prime_UTR	Exon 1 of 6	NP_001277182.1	Q8IYG9
	DPP6	NM_001364497.2		c.60+303721_60+303725delTTTTT		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.-92_-88delTTTTT		5_prime_UTR	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.-92_-88delTTTTT		5_prime_UTR	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000404039.5	TSL:1	c.51+164995_51+164999delTTTTT		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.000424 AC: 60 AN: 141452 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.0000517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000616

Gnomad OTH AF: 0.00103

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000381 AC: 38 AN: 997042 Hom.: 0 AF XY: 0.0000331 AC XY: 16 AN XY: 483722

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000557 AC: 1 AN: 17960

American (AMR) AF: 0.000283 AC: 4 AN: 14152

Ashkenazi Jewish (ASJ) AF: 0.0000885 AC: 1 AN: 11304

East Asian (EAS) AF: 0.0000948 AC: 1 AN: 10550

South Asian (SAS) AF: 0.0000543 AC: 3 AN: 55272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2654

European-Non Finnish (NFE) AF: 0.0000322 AC: 27 AN: 839250

Other (OTH) AF: 0.0000287 AC: 1 AN: 34898

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000424 AC: 60 AN: 141442 Hom.: 0 Cov.: 6 AF XY: 0.000439 AC XY: 30 AN XY: 68388

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000516 AC: 2 AN: 38748

American (AMR) AF: 0.00105 AC: 15 AN: 14352

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 4650

South Asian (SAS) AF: 0.00 AC: 0 AN: 4424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.000616 AC: 40 AN: 64960

Other (OTH) AF: 0.00102 AC: 2 AN: 1958

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.041
Mutation Taster		=297/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs571183490; hg19: chr7-153749805;