Variant 6-132297863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015529.4(MOXD1):c.1601G>A(p.Gly534Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MOXD1
NM_015529.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOXD1	NM_015529.4 linkuse as main transcript	c.1601G>A	p.Gly534Asp	missense_variant	11/12	ENST00000367963.8	NP_056344.2	Q6UVY6-1
MOXD1	XM_017010714.3 linkuse as main transcript	c.1496G>A	p.Gly499Asp	missense_variant	11/12		XP_016866203.1
MOXD1	XM_047418621.1 linkuse as main transcript	c.1340G>A	p.Gly447Asp	missense_variant	11/12		XP_047274577.1
MOXD1	XM_047418622.1 linkuse as main transcript	c.1340G>A	p.Gly447Asp	missense_variant	11/12		XP_047274578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOXD1	ENST00000367963.8 linkuse as main transcript	c.1601G>A	p.Gly534Asp	missense_variant	11/12	1	NM_015529.4	ENSP00000356940.3		Q6UVY6-1
MOXD1	ENST00000336749.3 linkuse as main transcript	c.1397G>A	p.Gly466Asp	missense_variant	10/11	1		ENSP00000336998.3		Q6UVY6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461228

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.1601G>A (p.G534D) alteration is located in exon 11 (coding exon 11) of the MOXD1 gene. This alteration results from a G to A substitution at nucleotide position 1601, causing the glycine (G) at amino acid position 534 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.5

D;N

REVEL

Benign

0.29

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.83

MutPred

0.46

Loss of helix (P = 0.0068);.;

MVP

0.54

MPC

0.25

ClinPred

0.96

GERP RS

6.1

Varity_R

0.45

gMVP

0.90

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