19-57166826-G-A

Position:

• chr19-57166826-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012729.2(DUXA):​c.25+593C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,110 control chromosomes in the GnomAD database, including 4,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4597 hom., cov: 32)
• Consequence: DUXA NM_001012729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

Genes affected

DUXA (HGNC:32179): (double homeobox A) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the DUXA homeobox gene family. Evidence of mRNA expression has not yet been found for this gene. Multiple, related processed pseudogenes have been found which are thought to reflect expression of this gene in the germ line or embryonic cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUXA	NM_001012729.2	c.25+593C>T		intron_variant		ENST00000554048.3	NP_001012747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUXA	ENST00000554048.3	c.25+593C>T		intron_variant		3	NM_001012729.2	ENSP00000452398.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36684 AN: 151992 Hom.: 4587 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36732 AN: 152110 Hom.: 4597 Cov.: 32 AF XY: 0.240 AC XY: 17825 AN XY: 74364

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.269

Alfa AF: 0.244 Hom.: 7436

Bravo AF: 0.251

Asia WGS AF: 0.289 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs11672517; hg19: chr19-57678194;