dbSNP rs12657132: DMXL1:c.8467-620C>G (chr5-119236702-C-G) – 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.8467-620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,576 control chromosomes in the GnomAD database, including 17,651 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 0.44 ( 17651 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

DMXL1
NM_001290321.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.249

Publications

1 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:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 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.8467-620C>G	intron	N/A	NP_001277250.1	F5H269
DMXL1	NM_001349239.2		c.8467-620C>G	intron	N/A	NP_001336168.1	F5H269
DMXL1	NM_001349240.2		c.8404-620C>G	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.8467-620C>G	intron	N/A	ENSP00000439479.1	F5H269
DMXL1	ENST00000311085.8	TSL:1	c.8404-620C>G	intron	N/A	ENSP00000309690.8	Q9Y485
DMXL1	ENST00000505312.5	TSL:1	n.941-620C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

66942

AN:

151458

Hom.:

17648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.421

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.442

AC:

66958

AN:

151576

Hom.:

17651

Cov.:

AF XY:

0.450

AC XY:

33326

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.164

AC:

6775

AN:

41398

American (AMR)

AF:

0.554

AC:

8436

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1381

AN:

3470

East Asian (EAS)

AF:

0.948

AC:

4909

AN:

5178

South Asian (SAS)

AF:

0.602

AC:

2891

AN:

4806

European-Finnish (FIN)

AF:

0.557

AC:

5855

AN:

10508

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35089

AN:

67670

Other (OTH)

AF:

0.422

AC:

892

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1632

3264

4897

6529

8161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.480

Hom.:

2377

Bravo

AF:

0.429

Asia WGS

AF:

0.716

AC:

2484

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

(source)

DANN

Benign

0.60

PhyloP100

-0.25

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over