6-132297302-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015529.4(MOXD1):c.1693G>T(p.Ala565Ser) 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. 13/21 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: 3.28

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

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=0.15652645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOXD1	NM_015529.4	c.1693G>T	p.Ala565Ser	missense_variant	12/12	ENST00000367963.8
MOXD1	XM_017010714.3	c.1588G>T	p.Ala530Ser	missense_variant	12/12
MOXD1	XM_047418621.1	c.1432G>T	p.Ala478Ser	missense_variant	12/12
MOXD1	XM_047418622.1	c.1432G>T	p.Ala478Ser	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOXD1	ENST00000367963.8	c.1693G>T	p.Ala565Ser	missense_variant	12/12	1	NM_015529.4	P1
MOXD1	ENST00000336749.3	c.1489G>T	p.Ala497Ser	missense_variant	11/11	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 27, 2023

The c.1693G>T (p.A565S) alteration is located in exon 12 (coding exon 12) of the MOXD1 gene. This alteration results from a G to T substitution at nucleotide position 1693, causing the alanine (A) at amino acid position 565 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	20
Dann	Uncertain	0.98
DEOGEN2	Benign	0.070	T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	0.58	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.12
Sift	Benign	0.23	T;T
Sift4G	Uncertain	0.041	D;D
Polyphen		0.48	P;P
Vest4		0.38
MutPred		0.28		Gain of disorder (P = 0.0292);.;
MVP		0.31
MPC		0.047
ClinPred		0.68	D
GERP RS		5.8
Varity_R		0.11
gMVP		0.39

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: chr6-132618441;