rs11672517

Variant names:

• chr19-57166826-G-A
• rs11672517
• NM_001012729.2:c.25+593C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DUXA	NM_001012729.2	c.25+593C>T		intron_variant	Intron 1 of 5	ENST00000554048.3	NP_001012747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUXA	ENST00000554048.3	c.25+593C>T		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.246 AC: 10205 AN: 41460

American (AMR) AF: 0.275 AC: 4195 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1086 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1477 AN: 5178

South Asian (SAS) AF: 0.276 AC: 1334 AN: 4830

European-Finnish (FIN) AF: 0.151 AC: 1598 AN: 10584

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16046 AN: 68002

Other (OTH) AF: 0.269 AC: 569 AN: 2114

Alfa AF: 0.242 Hom.: 17193

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
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11672517; hg19: chr19-57678194;