6-132302045-C-T

Variant names:

• chr6-132302045-C-T
• rs4897574
• NM_015529.4:c.1509-4090G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015529.4(MOXD1):​c.1509-4090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,880 control chromosomes in the GnomAD database, including 18,060 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 0.46 (18060 hom., cov: 32)
• Consequence: MOXD1 NM_015529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

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.1509-4090G>A		intron	N/A	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.1509-4090G>A		intron	N/A	ENSP00000356940.3	Q6UVY6-1
	MOXD1	ENST00000336749.3	TSL:1	c.1305-4090G>A		intron	N/A	ENSP00000336998.3	Q6UVY6-2
	MOXD1	ENST00000940886.1		c.1497-4090G>A		intron	N/A	ENSP00000610945.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70176 AN: 151762 Hom.: 18023 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.463 AC: 70257 AN: 151880 Hom.: 18060 Cov.: 32 AF XY: 0.462 AC XY: 34287 AN XY: 74212

African (AFR) AF: 0.681 AC: 28233 AN: 41428

American (AMR) AF: 0.398 AC: 6068 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3466

East Asian (EAS) AF: 0.685 AC: 3535 AN: 5158

South Asian (SAS) AF: 0.542 AC: 2608 AN: 4810

European-Finnish (FIN) AF: 0.338 AC: 3564 AN: 10556

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23907 AN: 67904

Other (OTH) AF: 0.431 AC: 910 AN: 2110

Alfa AF: 0.395 Hom.: 42472

Bravo AF: 0.477

Asia WGS AF: 0.603 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.50
DANN	Benign	0.41
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs4897574; hg19: chr6-132623184; COSMIC: COSV60942733;