Genetic Variant DMXL1:c.7458-32A>C (chr5-119196339-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001290321.3(DMXL1):c.7458-32A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,542,804 control chromosomes in the GnomAD database, including 336,409 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 0.65 ( 32909 hom., cov: 30)

Exomes 𝑓: 0.66 ( 303500 hom. )

Consequence

DMXL1
NM_001290321.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.936

Publications

13 publications found

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

new If you want to explore the variant's impact on the transcript NM_001290321.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMXL1	NM_001290321.3	MANE Select	c.7458-32A>C	intron	N/A	NP_001277250.1	F5H269
DMXL1	NM_001349239.2		c.7458-32A>C	intron	N/A	NP_001336168.1	F5H269
DMXL1	NM_001349240.2		c.7458-32A>C	intron	N/A	NP_001336169.1	Q9Y485

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.7458-32A>C	intron	N/A	ENSP00000439479.1	F5H269
DMXL1	ENST00000311085.8	TSL:1	c.7458-32A>C	intron	N/A	ENSP00000309690.8	Q9Y485
DMXL1	ENST00000939842.1		c.6060-32A>C	intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99033

AN:

151794

Hom.:

32873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.725

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.970

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.731

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.590

GnomAD2 exomes

AF:

0.690

AC:

173126

AN:

250976

AF XY:

0.685

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.782

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.969

Gnomad FIN exome

AF:

0.729

Gnomad NFE exome

AF:

0.634

Gnomad OTH exome

AF:

0.633

GnomAD4 exome

AF:

0.656

AC:

912612

AN:

1390892

Hom.:

303500

Cov.:

AF XY:

0.657

AC XY:

457244

AN XY:

696244

show subpopulations

African (AFR)

AF:

0.601

AC:

19302

AN:

32138

American (AMR)

AF:

0.771

AC:

34368

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

12753

AN:

25634

East Asian (EAS)

AF:

0.980

AC:

38560

AN:

39340

South Asian (SAS)

AF:

0.718

AC:

60925

AN:

84864

European-Finnish (FIN)

AF:

0.723

AC:

38530

AN:

53314

Middle Eastern (MID)

AF:

0.515

AC:

2901

AN:

5628

European-Non Finnish (NFE)

AF:

0.638

AC:

668437

AN:

1047364

Other (OTH)

AF:

0.635

AC:

36836

AN:

58010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

15305

30610

45915

61220

76525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17376

34752

52128

69504

86880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.653

AC:

99123

AN:

151912

Hom.:

32909

Cov.:

AF XY:

0.660

AC XY:

49030

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.603

AC:

24959

AN:

41416

American (AMR)

AF:

0.692

AC:

10560

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1728

AN:

3470

East Asian (EAS)

AF:

0.970

AC:

5018

AN:

5174

South Asian (SAS)

AF:

0.733

AC:

3535

AN:

4820

European-Finnish (FIN)

AF:

0.731

AC:

7707

AN:

10540

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.641

AC:

43561

AN:

67928

Other (OTH)

AF:

0.590

AC:

1243

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1688

3376

5065

6753

8441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.630

Hom.:

84673

Bravo

AF:

0.645

Asia WGS

AF:

0.814

AC:

2830

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.14

(source)

DANN

Benign

0.38

PhyloP100

-0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over