dbSNP rs116348108: DMXL1:c.213+1328A>G (chr5-119099432-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001290321.3(DMXL1):c.213+1328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,210 control chromosomes in the GnomAD database, including 68 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 0.022 ( 68 hom., cov: 32)

Consequence

DMXL1
NM_001290321.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

6 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=-0.92).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0222 (3374/152210) while in subpopulation NFE AF = 0.038 (2587/67996). AF 95% confidence interval is 0.0368. There are 68 homozygotes in GnomAd4. There are 1548 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 68 gene

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
DMXL1	NM_001290321.3	MANE Select	c.213+1328A>G	intron	N/A	NP_001277250.1
DMXL1	NM_001349239.2		c.213+1328A>G	intron	N/A	NP_001336168.1
DMXL1	NM_001349240.2		c.213+1328A>G	intron	N/A	NP_001336169.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.213+1328A>G	intron	N/A	ENSP00000439479.1
DMXL1	ENST00000311085.8	TSL:1	c.213+1328A>G	intron	N/A	ENSP00000309690.8
DMXL1	ENST00000503802.5	TSL:1	c.213+1328A>G	intron	N/A	ENSP00000427692.1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3374

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00601

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0222

AC:

3374

AN:

152210

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1548

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00599

AC:

249

AN:

41550

American (AMR)

AF:

0.0152

AC:

232

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00311

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0153

AC:

162

AN:

10590

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0380

AC:

2587

AN:

67996

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

175

350

524

699

874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0239

Hom.:

Bravo

AF:

0.0221

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.2

(source)

DANN

Benign

0.49

PhyloP100

-0.0090

Mutation Taster

=100/0

polymorphism

(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