rs6902875

Variant names:

• chr6-132295933-A-G
• rs6902875
• NM_015529.4:c.*1220T>C

Variant summary

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

The NM_015529.4(MOXD1):​c.*1220T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,056 control chromosomes in the GnomAD database, including 18,987 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 0.44 (18987 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MOXD1 NM_015529.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOXD1	NM_015529.4	c.*1220T>C		downstream_gene_variant		ENST00000367963.8	NP_056344.2
MOXD1	XM_017010714.3	c.*1220T>C		downstream_gene_variant			XP_016866203.1
MOXD1	XM_047418621.1	c.*1220T>C		downstream_gene_variant			XP_047274577.1
MOXD1	XM_047418622.1	c.*1220T>C		downstream_gene_variant			XP_047274578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOXD1	ENST00000367963.8	c.*1220T>C		downstream_gene_variant		1	NM_015529.4	ENSP00000356940.3
MOXD1	ENST00000336749.3	c.*1220T>C		downstream_gene_variant		1		ENSP00000336998.3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66184 AN: 151938 Hom.: 18934 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.386

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.436 AC: 66286 AN: 152056 Hom.: 18987 Cov.: 32 AF XY: 0.429 AC XY: 31892 AN XY: 74320

African (AFR) AF: 0.819 AC: 33991 AN: 41500

American (AMR) AF: 0.290 AC: 4421 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1548 AN: 5176

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4816

European-Finnish (FIN) AF: 0.290 AC: 3065 AN: 10562

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19628 AN: 67944

Other (OTH) AF: 0.391 AC: 824 AN: 2110

Alfa AF: 0.325 Hom.: 15774

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6902875; hg19: chr6-132617072; COSMIC: COSV60948306;