Genetic Variant DACH1:p.Pro16Leu (chr13-71866723-G-A) – ACMG Classification: Uncertain_significance (0 pts)

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>T(p.Pro16Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000774 in 1,292,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

DACH1
NM_080759.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

DACH1 links:

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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=0.16015106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6 link	c.47C>T	p.Pro16Leu	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
DACH1	ENST00000613252.5 link	c.47C>T	p.Pro16Leu	missense_variant	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1		Q9UI36-2
DACH1	ENST00000619232.2 link	c.47C>T	p.Pro16Leu	missense_variant	Exon 1 of 12	5		ENSP00000482797.1		Q9UI36-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

160116

AF XY:

0.00

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

AF:

7.74e-7

AC:

AN:

1292100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

636178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27348

American (AMR)

AF:

0.00

AC:

AN:

28842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20024

East Asian (EAS)

AF:

0.00

AC:

AN:

31788

South Asian (SAS)

AF:

0.00

AC:

AN:

57868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5044

European-Non Finnish (NFE)

AF:

9.79e-7

AC:

AN:

1021840

Other (OTH)

AF:

0.00

AC:

AN:

52044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

.;.;.;D

Eigen

Benign

-0.077

Eigen_PC

Benign

0.017

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

N;N;N;N

PhyloP100

4.2

PrimateAI

Pathogenic

0.87

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.31

B;B;B;.

Vest4

0.40

MutPred

0.14

Loss of catalytic residue at P15 (P = 0.0463);Loss of catalytic residue at P15 (P = 0.0463);Loss of catalytic residue at P15 (P = 0.0463);Loss of catalytic residue at P15 (P = 0.0463);

MVP

0.093

ClinPred

0.58

GERP RS

3.4

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.21

gMVP

0.32

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over