chr13-71479283-C-T

Position:

• chr13-71479283-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080759.6(DACH1):​c.1756G>A​(p.Ala586Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DACH1 NM_080759.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACH1	NM_080759.6	c.1756G>A	p.Ala586Thr	missense_variant	8/11	ENST00000613252.5	NP_542937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACH1	ENST00000613252.5	c.1756G>A	p.Ala586Thr	missense_variant	8/11	1	NM_080759.6	ENSP00000482245.1
DACH1	ENST00000619232.2	c.1912G>A	p.Ala638Thr	missense_variant	9/12	5		ENSP00000482797.1
DACH1	ENST00000706274.1	c.1135G>A	p.Ala379Thr	missense_variant	7/10			ENSP00000516320.1
DACH1	ENST00000706275.1	c.733G>A	p.Ala245Thr	missense_variant	7/10			ENSP00000516321.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.1762G>A (p.A588T) alteration is located in exon 8 (coding exon 8) of the DACH1 gene. This alteration results from a G to A substitution at nucleotide position 1762, causing the alanine (A) at amino acid position 588 to be replaced by a threonine (T). 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	0.28
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	.;.;.;D
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.92	P;D;D;.
Vest4		0.66
MutPred		0.23		Loss of helix (P = 0.0237);.;.;.;
MVP		0.58
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.37
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-72053415;