5-119165286-TA-T

Variant names:

• chr5-119165286-TA-T
• rs11301800
• NM_001290321.3:c.4970+24delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000539542.6(DMXL1):​c.4970+7delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (3934 hom., cov: 0)
  • Exomes 𝑓: 0.26 (464 hom.)
• Consequence: DMXL1 ENST00000539542.6 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.401
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-119165286-TA-T is Benign according to our data. Variant chr5-119165286-TA-T is described in ClinVar as Benign. ClinVar VariationId is 402595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539542.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMXL1	NM_001290321.3	MANE Select	c.4970+24delA		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.4970+24delA		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.4970+24delA		intron	N/A	NP_001336169.1	Q9Y485

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.4970+7delA		splice_region intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.4970+7delA		splice_region intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.4325+7delA		splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 32513 AN: 114172 Hom.: 3934 Cov.: 0

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.270

GnomAD2 exomes AF: 0.238 AC: 20661 AN: 86686 AF XY: 0.232

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.257 AC: 196559 AN: 764058 Hom.: 464 Cov.: 0 AF XY: 0.254 AC XY: 100500 AN XY: 395466

African (AFR) AF: 0.271 AC: 4797 AN: 17680

American (AMR) AF: 0.214 AC: 4702 AN: 21966

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 3970 AN: 16438

East Asian (EAS) AF: 0.326 AC: 10398 AN: 31864

South Asian (SAS) AF: 0.189 AC: 8943 AN: 47254

European-Finnish (FIN) AF: 0.244 AC: 9193 AN: 37616

Middle Eastern (MID) AF: 0.250 AC: 655 AN: 2618

European-Non Finnish (NFE) AF: 0.261 AC: 144828 AN: 554166

Other (OTH) AF: 0.263 AC: 9073 AN: 34456

GnomAD4 genome AF: 0.285 AC: 32514 AN: 114164 Hom.: 3934 Cov.: 0 AF XY: 0.286 AC XY: 15620 AN XY: 54634

African (AFR) AF: 0.308 AC: 9397 AN: 30468

American (AMR) AF: 0.296 AC: 3381 AN: 11438

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 729 AN: 2816

East Asian (EAS) AF: 0.511 AC: 2307 AN: 4518

South Asian (SAS) AF: 0.177 AC: 637 AN: 3598

European-Finnish (FIN) AF: 0.315 AC: 1756 AN: 5578

Middle Eastern (MID) AF: 0.271 AC: 58 AN: 214

European-Non Finnish (NFE) AF: 0.258 AC: 13741 AN: 53266

Other (OTH) AF: 0.268 AC: 429 AN: 1602

Alfa AF: 0.0591 Hom.: 74

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11301800; hg19: chr5-118500981; COSMIC: COSV60708825; COSMIC: COSV60708825;