Variant 5-119116201-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001290321.3(DMXL1):c.608G>A(p.Arg203Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000399 in 1,613,336 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 3 hom. )

Consequence

DMXL1
NM_001290321.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067194104).

BP6

Variant 5-119116201-G-A is Benign according to our data. Variant chr5-119116201-G-A is described in ClinVar as [Benign]. Clinvar id is 3049987.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL1	NM_001290321.3 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	7/44	ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DMXL1	ENST00000539542.6 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	7/44	1	NM_001290321.3	ENSP00000439479	A1
DMXL1	ENST00000311085.8 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	7/43	1		ENSP00000309690	P3
DMXL1	ENST00000503802.5 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	8/13	1		ENSP00000427692
DMXL1	ENST00000514151.1 linkuse as main transcript	n.280G>A		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.000553

AC:

AN:

151794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000756

AC:

190

AN:

251290

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000383

AC:

560

AN:

1461424

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

277

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000553

AC:

AN:

151912

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000700

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000745

Hom.:

Bravo

AF:

0.000725

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000585

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMXL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

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

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0067

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

0.96

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.42

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.38

T;T;T

Sift4G

Uncertain

0.024

D;.;.

Polyphen

0.98, 0.93

.;D;P

Vest4

0.22, 0.24

MVP

0.45

MPC

0.064

ClinPred

0.022

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.22

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