rs599660

Positions:

• chr6-132320536-T-C
• chr6-132320536-T-G

Variant summary

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

The NM_015529.4(MOXD1):​c.1365+93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,079,844 control chromosomes in the GnomAD database, including 101,190 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 0.51 (23826 hom., cov: 32)
  • Exomes 𝑓: 0.39 (77364 hom.)
• Consequence: MOXD1 NM_015529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOXD1	NM_015529.4	c.1365+93A>G		intron_variant		ENST00000367963.8
MOXD1	XM_017010714.3	c.1260+93A>G		intron_variant
MOXD1	XM_047418621.1	c.1104+93A>G		intron_variant
MOXD1	XM_047418622.1	c.1104+93A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOXD1	ENST00000367963.8	c.1365+93A>G		intron_variant		1	NM_015529.4	P1
MOXD1	ENST00000336749.3	c.1161+93A>G		intron_variant		1
MOXD1	ENST00000489128.1	n.487+93A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78140 AN: 151882 Hom.: 23771 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.393 AC: 364304 AN: 927844 Hom.: 77364 AF XY: 0.394 AC XY: 184873 AN XY: 468630

Gnomad4 AFR exome AF: 0.862

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.680

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.515 AC: 78244 AN: 152000 Hom.: 23826 Cov.: 32 AF XY: 0.512 AC XY: 38056 AN XY: 74270

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.473

Alfa AF: 0.468 Hom.: 2612

Bravo AF: 0.536

Asia WGS AF: 0.615 AC: 2133 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.74

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: rs599660; hg19: chr6-132641675;