6-132322698-T-C

Position:

• chr6-132322698-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015529.4(MOXD1):​c.1286A>G​(p.Glu429Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOXD1 NM_015529.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOXD1	NM_015529.4	c.1286A>G	p.Glu429Gly	missense_variant	8/12	ENST00000367963.8	NP_056344.2
MOXD1	XM_017010714.3	c.1181A>G	p.Glu394Gly	missense_variant	8/12		XP_016866203.1
MOXD1	XM_047418621.1	c.1025A>G	p.Glu342Gly	missense_variant	8/12		XP_047274577.1
MOXD1	XM_047418622.1	c.1025A>G	p.Glu342Gly	missense_variant	8/12		XP_047274578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOXD1	ENST00000367963.8	c.1286A>G	p.Glu429Gly	missense_variant	8/12	1	NM_015529.4	ENSP00000356940.3
MOXD1	ENST00000336749.3	c.1082A>G	p.Glu361Gly	missense_variant	7/11	1		ENSP00000336998.3
MOXD1	ENST00000489128.1	n.408A>G		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2024

The c.1286A>G (p.E429G) alteration is located in exon 8 (coding exon 8) of the MOXD1 gene. This alteration results from a A to G substitution at nucleotide position 1286, causing the glutamic acid (E) at amino acid position 429 to be replaced by a glycine (G). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.95	P;D
Vest4		0.67
MutPred		0.34		Loss of solvent accessibility (P = 0.0769);.;
MVP		0.86
MPC		0.22
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.44
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-132643837;