Genetic Variant DMXL1:p.Val195Val (chr5-119116178-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001290321.3(DMXL1):c.585T>G(p.Val195Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,611,728 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.039 ( 316 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 441 hom. )

Consequence

DMXL1
NM_001290321.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.210

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-119116178-T-G is Benign according to our data. Variant chr5-119116178-T-G is described in ClinVar as [Benign]. Clinvar id is 3059735.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMXL1	NM_001290321.3 link	c.585T>G	p.Val195Val	synonymous_variant	Exon 7 of 44	ENST00000539542.6	NP_001277250.1	Q9Y485B2RWN7F5H269F1T0K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DMXL1	ENST00000539542.6 link	c.585T>G	p.Val195Val	synonymous_variant	Exon 7 of 44	1	NM_001290321.3	ENSP00000439479.1	F5H269
DMXL1	ENST00000311085.8 link	c.585T>G	p.Val195Val	synonymous_variant	Exon 7 of 43	1		ENSP00000309690.8	Q9Y485
DMXL1	ENST00000503802.5 link	c.585T>G	p.Val195Val	synonymous_variant	Exon 8 of 13	1		ENSP00000427692.1	E7EMZ0
DMXL1	ENST00000514151.1 link	n.257T>G		non_coding_transcript_exon_variant	Exon 4 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5975

AN:

152062

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0316

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0198

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0212

AC:

5309

AN:

250492

Hom.:

197

AF XY:

0.0182

AC XY:

2463

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.0483

Gnomad ASJ exome

AF:

0.00578

Gnomad EAS exome

AF:

0.0229

Gnomad SAS exome

AF:

0.0328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000529

Gnomad OTH exome

AF:

0.0141

GnomAD4 exome

AF:

0.00777

AC:

11347

AN:

1459548

Hom.:

441

Cov.:

AF XY:

0.00796

AC XY:

5778

AN XY:

726074

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.0474

Gnomad4 ASJ exome

AF:

0.00507

Gnomad4 EAS exome

AF:

0.0156

Gnomad4 SAS exome

AF:

0.0329

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000472

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0394

AC:

5998

AN:

152180

Hom.:

316

Cov.:

AF XY:

0.0400

AC XY:

2977

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.0316

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.0200

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.00939

Hom.:

Bravo

AF:

0.0463

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMXL1-related disorder

Benign:1

Feb 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.4

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over