rs589756

chr6-132321978-C-Achr6-132321978-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015529.4(MOXD1):c.1305+701G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,088 control chromosomes in the GnomAD database, including 2,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2436 hom., cov: 32)
• Consequence: MOXD1 NM_015529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOXD1	NM_015529.4	c.1305+701G>T		intron_variant		ENST00000367963.8
MOXD1	XM_017010714.3	c.1200+701G>T		intron_variant
MOXD1	XM_047418621.1	c.1044+701G>T		intron_variant
MOXD1	XM_047418622.1	c.1044+701G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOXD1	ENST00000367963.8	c.1305+701G>T		intron_variant		1	NM_015529.4	P1
MOXD1	ENST00000336749.3	c.1101+701G>T		intron_variant		1
MOXD1	ENST00000489128.1	n.427+701G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26596 AN: 151970 Hom.: 2437 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26592 AN: 152088 Hom.: 2436 Cov.: 32 AF XY: 0.168 AC XY: 12516 AN XY: 74370

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.155

Alfa AF: 0.199 Hom.: 5234

Bravo AF: 0.173

Asia WGS AF: 0.0500 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs589756; hg19: chr6-132643117; COSMIC: COSV60942867;