13-71866723-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080759.6(DACH1):​c.47C>G​(p.Pro16Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Consequence

DACH1
NM_080759.6 missense

Scores

2
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

Publications

0 publications found
Variant links:
Genes affected
DACH1 (HGNC:2663): (dachshund family transcription factor 1) This gene encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression and cell fate determination during development. The protein contains a Ski domain that is highly conserved from Drosophila to human. Expression of this gene is lost in some forms of metastatic cancer, and is correlated with poor prognosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2098082).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DACH1NM_080759.6 linkc.47C>G p.Pro16Arg missense_variant Exon 1 of 11 ENST00000613252.5 NP_542937.3 Q9UI36-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DACH1ENST00000613252.5 linkc.47C>G p.Pro16Arg missense_variant Exon 1 of 11 1 NM_080759.6 ENSP00000482245.1 Q9UI36-2
DACH1ENST00000619232.2 linkc.47C>G p.Pro16Arg missense_variant Exon 1 of 12 5 ENSP00000482797.1 Q9UI36-1

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
29

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.47C>G (p.P16R) alteration is located in exon 1 (coding exon 1) of the DACH1 gene. This alteration results from a C to G substitution at nucleotide position 47, causing the proline (P) at amino acid position 16 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.24
.;.;.;T
Eigen
Benign
0.15
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.75
T;T;T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
0.69
N;N;N;N
PhyloP100
4.2
PrimateAI
Pathogenic
0.86
D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.87
P;P;P;.
Vest4
0.47
MutPred
0.10
Loss of catalytic residue at P15 (P = 0.0258);Loss of catalytic residue at P15 (P = 0.0258);Loss of catalytic residue at P15 (P = 0.0258);Loss of catalytic residue at P15 (P = 0.0258);
MVP
0.12
ClinPred
0.54
D
GERP RS
3.4
PromoterAI
-0.087
Neutral
Varity_R
0.20
gMVP
0.43
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs1351443893; hg19: chr13-72440861; API