6-132322762-T-C

Position:

• chr6-132322762-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 in silico tools predict a benign outcome for this variant. 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: 2.44

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOXD1	NM_015529.4	c.1222A>G	p.Met408Val	missense_variant	8/12	ENST00000367963.8	NP_056344.2
MOXD1	XM_017010714.3	c.1117A>G	p.Met373Val	missense_variant	8/12		XP_016866203.1
MOXD1	XM_047418621.1	c.961A>G	p.Met321Val	missense_variant	8/12		XP_047274577.1
MOXD1	XM_047418622.1	c.961A>G	p.Met321Val	missense_variant	8/12		XP_047274578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOXD1	ENST00000367963.8	c.1222A>G	p.Met408Val	missense_variant	8/12	1	NM_015529.4	ENSP00000356940.3
MOXD1	ENST00000336749.3	c.1018A>G	p.Met340Val	missense_variant	7/11	1		ENSP00000336998.3
MOXD1	ENST00000489128.1	n.344A>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

Jul 02, 2024

The c.1222A>G (p.M408V) 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 1222, causing the methionine (M) at amino acid position 408 to be replaced by a valine (V). 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	0.083
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;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.51	N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.14
Sift	Benign	0.71	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0010	B;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-132643901;