Variant chr13-71557102-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080759.6(DACH1):c.1492G>A(p.Val498Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,612,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

DACH1
NM_080759.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032133877).

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH1	NM_080759.6 linkuse as main transcript	c.1492G>A	p.Val498Ile	missense_variant	6/11	ENST00000613252.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH1	ENST00000613252.5 linkuse as main transcript	c.1492G>A	p.Val498Ile	missense_variant	6/11	1	NM_080759.6	P2	Q9UI36-2
DACH1	ENST00000619232.2 linkuse as main transcript	c.1648G>A	p.Val550Ile	missense_variant	7/12	5		A2	Q9UI36-1
DACH1	ENST00000706274.1 linkuse as main transcript	c.874G>A	p.Val292Ile	missense_variant	5/10
DACH1	ENST00000706275.1 linkuse as main transcript	c.469G>A	p.Val157Ile	missense_variant	5/10

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000566

AC:

AN:

247328

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134240

show subpopulations

Gnomad AFR exome

AF:

0.000719

Gnomad AMR exome

AF:

0.0000588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1460016

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726306

show subpopulations

Gnomad4 AFR exome

AF:

0.000571

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000309

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.000990

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000989

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00105

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000579

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2023

The c.1498G>A (p.V500I) alteration is located in exon 6 (coding exon 6) of the DACH1 gene. This alteration results from a G to A substitution at nucleotide position 1498, causing the valine (V) at amino acid position 500 to be replaced by an isoleucine (I). 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

0.079

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0019

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.90

D;D;D;D

PrimateAI

Uncertain

0.60

Sift4G

Benign

0.55

T;T

Polyphen

0.0020

B;.

Vest4

0.26

MVP

0.043

ClinPred

0.076

GERP RS

4.9

Varity_R

0.054

gMVP

0.12

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