chr6-132322762-T-C

Variant names:

• chr6-132322762-T-C
• NM_015529.4:c.1222A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015529.4(MOXD1):​c.1222A>G​(p.Met408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOXD1 NM_015529.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098944485).

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.1222A>G	p.Met408Val	missense	Exon 8 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.1222A>G	p.Met408Val	missense	Exon 8 of 12	ENSP00000356940.3	Q6UVY6-1
	MOXD1	ENST00000336749.3	TSL:1	c.1018A>G	p.Met340Val	missense	Exon 7 of 11	ENSP00000336998.3	Q6UVY6-2
	MOXD1	ENST00000940886.1		c.1210A>G	p.Met404Val	missense	Exon 8 of 12	ENSP00000610945.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.51	N
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.71	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.28
MutPred		0.54		Gain of methylation at K409 (P = 0.029)
MVP		0.34
MPC		0.037
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.052
gMVP		0.32
Mutation Taster		=85/15	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

hg19: chr6-132643901;