rs1538308

Positions:

• chr6-132377317-G-A
• chr6-132377317-G-T

Variant summary

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

The NM_015529.4(MOXD1):​c.265-2540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,146 control chromosomes in the GnomAD database, including 1,821 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 0.13 (1821 hom., cov: 32)
• Consequence: MOXD1 NM_015529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOXD1	NM_015529.4	c.265-2540C>T		intron_variant		ENST00000367963.8
MOXD1	XM_017010714.3	c.160-2540C>T		intron_variant
MOXD1	XM_047418621.1	c.4-2540C>T		intron_variant
MOXD1	XM_047418622.1	c.4-2540C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOXD1	ENST00000367963.8	c.265-2540C>T		intron_variant		1	NM_015529.4	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19320 AN: 152028 Hom.: 1820 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.127 AC: 19356 AN: 152146 Hom.: 1821 Cov.: 32 AF XY: 0.133 AC XY: 9876 AN XY: 74390

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0951 Hom.: 414

Bravo AF: 0.137

Asia WGS AF: 0.244 AC: 846 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.17

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: rs1538308; hg19: chr6-132698456;