Genetic Variant MOXD1:c.-40A>C (chr6-132374877-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000336749.3(MOXD1):c.-40A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,214,052 control chromosomes in the GnomAD database, including 30,572 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 0.30 ( 10539 hom., cov: 33)

Exomes 𝑓: 0.17 ( 20033 hom. )

Consequence

MOXD1
ENST00000336749.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

Publications

5 publications found

Variant links:

Genes affected

MOXD1 (HGNC:21063): (monooxygenase DBH like 1) Predicted to enable copper ion binding activity and dopamine beta-monooxygenase activity. Predicted to be involved in dopamine catabolic process; norepinephrine biosynthetic process; and octopamine biosynthetic process. Part of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

MOXD1 links:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MOXD1	NM_015529.4 link	c.265-100A>C	intron_variant	Intron 1 of 11	ENST00000367963.8	NP_056344.2	Q6UVY6-1
MOXD1	XM_017010714.3 link	c.160-100A>C	intron_variant	Intron 1 of 11		XP_016866203.1
MOXD1	XM_047418621.1 link	c.4-100A>C	intron_variant	Intron 1 of 11		XP_047274577.1
MOXD1	XM_047418622.1 link	c.4-100A>C	intron_variant	Intron 1 of 11		XP_047274578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOXD1	ENST00000336749.3 link	c.-40A>C		5_prime_UTR_variant	Exon 1 of 11	1		ENSP00000336998.3		Q6UVY6-2
MOXD1	ENST00000367963.8 link	c.265-100A>C		intron_variant	Intron 1 of 11	1	NM_015529.4	ENSP00000356940.3		Q6UVY6-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45896

AN:

152014

Hom.:

10513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.277

GnomAD2 exomes

AF:

0.214

AC:

27396

AN:

127806

AF XY:

0.209

show subpopulations

Gnomad AFR exome

AF:

0.669

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.173

AC:

183926

AN:

1061920

Hom.:

20033

Cov.:

AF XY:

0.174

AC XY:

93171

AN XY:

535584

show subpopulations

African (AFR)

AF:

0.667

AC:

15980

AN:

23968

American (AMR)

AF:

0.158

AC:

4844

AN:

30590

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

3361

AN:

21414

East Asian (EAS)

AF:

0.224

AC:

7689

AN:

34348

South Asian (SAS)

AF:

0.246

AC:

16503

AN:

67142

European-Finnish (FIN)

AF:

0.137

AC:

6187

AN:

45288

Middle Eastern (MID)

AF:

0.210

AC:

728

AN:

3468

European-Non Finnish (NFE)

AF:

0.151

AC:

119173

AN:

789246

Other (OTH)

AF:

0.204

AC:

9461

AN:

46456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

7591

15181

22772

30362

37953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3916

7832

11748

15664

19580

<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:

0.302

AC:

45983

AN:

152132

Hom.:

10539

Cov.:

AF XY:

0.298

AC XY:

22152

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.645

AC:

26743

AN:

41462

American (AMR)

AF:

0.205

AC:

3132

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

566

AN:

3470

East Asian (EAS)

AF:

0.239

AC:

1238

AN:

5182

South Asian (SAS)

AF:

0.252

AC:

1214

AN:

4812

European-Finnish (FIN)

AF:

0.132

AC:

1402

AN:

10610

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10849

AN:

67986

Other (OTH)

AF:

0.282

AC:

595

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1317

2633

3950

5266

6583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.186

Hom.:

5979

Bravo

AF:

0.322

Asia WGS

AF:

0.318

AC:

1109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.3

(source)

DANN

Benign

0.55

PhyloP100

2.4

PromoterAI

0.010

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over