chr5-119196339-A-C

Position:

• chr5-119196339-A-C

Variant summary

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

The NM_001290321.3(DMXL1):​c.7458-32A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,542,804 control chromosomes in the GnomAD database, including 336,409 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 0.65 (32909 hom., cov: 30)
  • Exomes 𝑓: 0.66 (303500 hom.)
• Consequence: DMXL1 NM_001290321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

Genes affected

DMXL1 (HGNC:2937): (Dmx like 1) The protein encoded by this gene is a member of the WD repeat superfamily of proteins, which have regulatory functions. This gene is expressed in many tissue types including several types of eye tissue, and it has been associated with ocular phenotypes. In addition, it is upregulated in cultured cells that overexpress growth factor independence 1B, a transcription factor that is essential for hematopoietic cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

DMXL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL1	NM_001290321.3	c.7458-32A>C		intron_variant		ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMXL1	ENST00000539542.6	c.7458-32A>C		intron_variant		1	NM_001290321.3	ENSP00000439479.1
DMXL1	ENST00000311085.8	c.7458-32A>C		intron_variant		1		ENSP00000309690.8

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99033 AN: 151794 Hom.: 32873 Cov.: 30

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.590

GnomAD3 exomes AF: 0.690 AC: 173126 AN: 250976 Hom.: 61321 AF XY: 0.685 AC XY: 92851 AN XY: 135644

Gnomad AFR exome AF: 0.602

Gnomad AMR exome AF: 0.782

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.969

Gnomad SAS exome AF: 0.718

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.634

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.656 AC: 912612 AN: 1390892 Hom.: 303500 Cov.: 22 AF XY: 0.657 AC XY: 457244 AN XY: 696244

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.980

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.653 AC: 99123 AN: 151912 Hom.: 32909 Cov.: 30 AF XY: 0.660 AC XY: 49030 AN XY: 74238

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.590

Alfa AF: 0.623 Hom.: 48237

Bravo AF: 0.645

Asia WGS AF: 0.814 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.38

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: rs6595178; hg19: chr5-118532034;