rs11740134

chr5-119059022-G-Achr5-119059022-G-C

Variant summary

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

The ENST00000504820.2(DMXL1-DT):n.97+11784C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,150 control chromosomes in the GnomAD database, including 2,908 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 0.18 (2908 hom., cov: 32)
• Consequence: DMXL1-DT ENST00000504820.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

Genes affected

DMXL1-DT (HGNC:55568): (DMXL1 divergent transcript)

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMXL1-DT	NR_134250.1	n.85+11784C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMXL1-DT	ENST00000504820.2	n.97+11784C>T		intron_variant, non_coding_transcript_variant		4
DMXL1	ENST00000509902.5	n.226+14044G>A		intron_variant, non_coding_transcript_variant		3
DMXL1-DT	ENST00000510128.1	n.56+11784C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26707 AN: 152032 Hom.: 2907 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.175 AC: 26697 AN: 152150 Hom.: 2908 Cov.: 32 AF XY: 0.182 AC XY: 13502 AN XY: 74352

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.148

Alfa AF: 0.200 Hom.: 4130

Bravo AF: 0.158

Asia WGS AF: 0.295 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.30
Dann	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11740134; hg19: chr5-118394717;