rs786205143

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_130797.4(DPP6):​c.1153A>C​(p.Met385Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

DPP6
NM_130797.4 missense

Scores

2
12
4

Clinical Significance

no classifications from unflagged records no classifications from unflagged records P:1

Conservation

PhyloP100: 7.03
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.748
PP5
Variant 7-154794095-A-C is Pathogenic according to our data. Variant chr7-154794095-A-C is described in ClinVar as [no_classifications_from_unflagged_records]. Clinvar id is 189389.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DPP6NM_130797.4 linkuse as main transcriptc.1153A>C p.Met385Leu missense_variant 11/26 ENST00000377770.8 NP_570629.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DPP6ENST00000377770.8 linkuse as main transcriptc.1153A>C p.Met385Leu missense_variant 11/261 NM_130797.4 ENSP00000367001 P42658-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: no classifications from unflagged records
Submissions summary: Pathogenic:1
Revision: no classifications from unflagged records
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 33 Pathogenic:1
Pathogenic, flagged submissionliterature onlyOMIMSep 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Uncertain
0.093
D
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.034
.;T;.;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.91
D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.75
D;D;D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.8
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.7
D;D;D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.018
D;D;D;D
Sift4G
Uncertain
0.033
D;D;D;D
Polyphen
0.80
P;P;P;B
Vest4
0.89
MutPred
0.70
.;Loss of MoRF binding (P = 0.0907);.;.;
MVP
0.23
MPC
0.68
ClinPred
0.97
D
GERP RS
4.2
Varity_R
0.75
gMVP
0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs786205143; hg19: chr7-154585805; API