rs147224004
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003836.7(DLK1):āc.194A>Cā(p.His65Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
DLK1
NM_003836.7 missense
NM_003836.7 missense
Scores
5
9
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.52
Genes affected
DLK1 (HGNC:2907): (delta like non-canonical Notch ligand 1) This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.768
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DLK1 | ENST00000341267.9 | c.194A>C | p.His65Pro | missense_variant | Exon 3 of 5 | 1 | NM_003836.7 | ENSP00000340292.4 | ||
| DLK1 | ENST00000331224.10 | c.194A>C | p.His65Pro | missense_variant | Exon 3 of 6 | 1 | ENSP00000331081.6 | |||
| DLK1 | ENST00000556051.1 | c.194A>C | p.His65Pro | missense_variant | Exon 3 of 3 | 2 | ENSP00000450821.1 | |||
| DLK1 | ENST00000392848.9 | c.194A>C | p.His65Pro | missense_variant | Exon 5 of 6 | 4 | ENSP00000376589.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727230
GnomAD4 exome
AF:
AC:
1
AN:
1461838
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727230
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;D;D;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;T;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;M;M;M;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D
Sift4G
Uncertain
D;D;.;T;D
Polyphen
0.36, 0.90
.;B;B;P;.
Vest4
0.58, 0.56, 0.48
MutPred
Gain of catalytic residue at L64 (P = 0);Gain of catalytic residue at L64 (P = 0);Gain of catalytic residue at L64 (P = 0);Gain of catalytic residue at L64 (P = 0);Gain of catalytic residue at L64 (P = 0);
MVP
MPC
0.91
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.