chr5-119138414-A-G

Position:

• chr5-119138414-A-G

Variant summary

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

The NM_001290321.3(DMXL1):​c.2376+4025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,156 control chromosomes in the GnomAD database, including 5,342 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 (5342 hom., cov: 32)
• Consequence: DMXL1 NM_001290321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL1	NM_001290321.3	c.2376+4025A>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.2376+4025A>G		intron_variant		1	NM_001290321.3	ENSP00000439479	A1
DMXL1	ENST00000311085.8	c.2376+4025A>G		intron_variant		1		ENSP00000309690	P3
DMXL1	ENST00000512281.1	n.164+4025A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37241 AN: 152038 Hom.: 5342 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.245 AC: 37254 AN: 152156 Hom.: 5342 Cov.: 32 AF XY: 0.237 AC XY: 17648 AN XY: 74388

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.286

Alfa AF: 0.323 Hom.: 16949

Bravo AF: 0.239

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.80

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: rs4895185; hg19: chr5-118474109;