Variant 6-132320654-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015529.4(MOXD1):c.1340C>T(p.Thr447Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,609,722 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: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MOXD1
NM_015529.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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:

MOXD1 (HGNC:):

MOXD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOXD1	NM_015529.4 linkuse as main transcript	c.1340C>T	p.Thr447Met	missense_variant	9/12	ENST00000367963.8	NP_056344.2	Q6UVY6-1
MOXD1	XM_017010714.3 linkuse as main transcript	c.1235C>T	p.Thr412Met	missense_variant	9/12		XP_016866203.1
MOXD1	XM_047418621.1 linkuse as main transcript	c.1079C>T	p.Thr360Met	missense_variant	9/12		XP_047274577.1
MOXD1	XM_047418622.1 linkuse as main transcript	c.1079C>T	p.Thr360Met	missense_variant	9/12		XP_047274578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MOXD1	ENST00000367963.8 linkuse as main transcript	c.1340C>T	p.Thr447Met	missense_variant	9/12	1	NM_015529.4	ENSP00000356940.3	Q6UVY6-1
MOXD1	ENST00000336749.3 linkuse as main transcript	c.1136C>T	p.Thr379Met	missense_variant	8/11	1		ENSP00000336998.3	Q6UVY6-2
MOXD1	ENST00000489128.1 linkuse as main transcript	n.462C>T		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000564

AC:

AN:

248206

Hom.:

AF XY:

0.0000745

AC XY:

AN XY:

134174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

154

AN:

1457744

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

725128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151978

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000989

AC:

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

Nov 26, 2024

The c.1340C>T (p.T447M) alteration is located in exon 9 (coding exon 9) of the MOXD1 gene. This alteration results from a C to T substitution at nucleotide position 1340, causing the threonine (T) at amino acid position 447 to be replaced by a methionine (M). 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

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.77

D;.

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.3

D;D

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.97

MVP

0.78

MPC

0.23

ClinPred

0.92

GERP RS

5.6

Varity_R

0.49

gMVP

0.86

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