Variant 14-58638455-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001079520.2(DACT1):c.253C>A(p.Arg85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.989

Variant links:

Genes affected

DACT1 (HGNC:17748): (dishevelled binding antagonist of beta catenin 1) The protein encoded by this gene belongs to the dapper family, characterized by the presence of PDZ-binding motif at the C-terminus. It interacts with, and positively regulates dishevelled-mediated signaling pathways during development. Depletion of this mRNA from xenopus embryos resulted in loss of notochord and head structures, and mice lacking this gene died shortly after birth from severe posterior malformations. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

DACT1 links:

DACT1 (HGNC:):

DACT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36084557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACT1	NM_001079520.2 linkuse as main transcript	c.253C>A	p.Arg85Ser	missense_variant	1/4	ENST00000395153.8	NP_001072988.1	Q9NYF0-2
DACT1	NM_016651.6 linkuse as main transcript	c.253C>A	p.Arg85Ser	missense_variant	1/4		NP_057735.2	Q9NYF0-1
DACT1	NR_046093.2 linkuse as main transcript	n.126-2281C>A		intron_variant
DACT1	NR_165650.1 linkuse as main transcript	n.126-2281C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACT1	ENST00000395153.8 linkuse as main transcript	c.253C>A	p.Arg85Ser	missense_variant	1/4	5	NM_001079520.2	ENSP00000378582.3		Q9NYF0-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1199832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

580160

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DACT1-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 28, 2024

The DACT1 c.253C>A variant is predicted to result in the amino acid substitution p.Arg85Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

.;T

Eigen

Benign

0.11

Eigen_PC

Benign

-0.00033

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.57

T;T

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.12

Sift

Benign

0.13

T;T

Sift4G

Benign

0.39

T;T

Polyphen

1.0

.;D

Vest4

0.23

MutPred

0.28

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.36

MPC

0.68

ClinPred

0.95

GERP RS

3.4

Varity_R

0.23

gMVP

0.094

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over