5-119236702-C-G

Position:

• chr5-119236702-C-G

Variant summary

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

The NM_001290321.3(DMXL1):​c.8467-620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,576 control chromosomes in the GnomAD database, including 17,651 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 0.44 (17651 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DMXL1 NM_001290321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL1	NM_001290321.3	c.8467-620C>G		intron_variant		ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMXL1	ENST00000539542.6	c.8467-620C>G		intron_variant		1	NM_001290321.3	ENSP00000439479	A1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66942 AN: 151458 Hom.: 17648 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.421

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.442 AC: 66958 AN: 151576 Hom.: 17651 Cov.: 31 AF XY: 0.450 AC XY: 33326 AN XY: 74030

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.422

Alfa AF: 0.480 Hom.: 2377

Bravo AF: 0.429

Asia WGS AF: 0.716 AC: 2484 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.60

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: rs12657132; hg19: chr5-118572397; COSMIC: COSV60706164;