6-132315738-G-C

Variant names:

• chr6-132315738-G-C
• rs966635220
• NM_015529.4:c.1405C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015529.4(MOXD1):​c.1405C>G​(p.Leu469Val) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L469I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOXD1 NM_015529.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015529.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOXD1	NM_015529.4	MANE Select	c.1405C>G	p.Leu469Val	missense	Exon 10 of 12	NP_056344.2	Q6UVY6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOXD1	ENST00000367963.8	TSL:1 MANE Select	c.1405C>G	p.Leu469Val	missense	Exon 10 of 12	ENSP00000356940.3	Q6UVY6-1
	MOXD1	ENST00000336749.3	TSL:1	c.1201C>G	p.Leu401Val	missense	Exon 9 of 11	ENSP00000336998.3	Q6UVY6-2
	MOXD1	ENST00000940886.1		c.1393C>G	p.Leu465Val	missense	Exon 10 of 12	ENSP00000610945.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.41
Sift	Benign	0.062	T
Sift4G	Uncertain	0.026	D
Polyphen		0.87	P
Vest4		0.73
MutPred		0.31		Gain of catalytic residue at L469 (P = 0.064)
MVP		0.74
MPC		0.16
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.49
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs966635220; hg19: chr6-132636877;