6-132374877-T-G

Variant names:

• chr6-132374877-T-G
• rs3734744
• ENST00000336749.3:c.-40A>C

Variant summary

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

The ENST00000336749.3(MOXD1):​c.-40A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,214,052 control chromosomes in the GnomAD database, including 30,572 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 0.30 (10539 hom., cov: 33)
  • Exomes 𝑓: 0.17 (20033 hom.)
• Consequence: MOXD1 ENST00000336749.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336749.3. 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.265-100A>C		intron	N/A	NP_056344.2	Q6UVY6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOXD1	ENST00000336749.3	TSL:1	c.-40A>C		5_prime_UTR	Exon 1 of 11	ENSP00000336998.3	Q6UVY6-2
	MOXD1	ENST00000367963.8	TSL:1 MANE Select	c.265-100A>C		intron	N/A	ENSP00000356940.3	Q6UVY6-1
	MOXD1	ENST00000940886.1		c.265-100A>C		intron	N/A	ENSP00000610945.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45896 AN: 152014 Hom.: 10513 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.277

GnomAD2 exomes AF: 0.214 AC: 27396 AN: 127806 AF XY: 0.209

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.261

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.173 AC: 183926 AN: 1061920 Hom.: 20033 Cov.: 14 AF XY: 0.174 AC XY: 93171 AN XY: 535584

African (AFR) AF: 0.667 AC: 15980 AN: 23968

American (AMR) AF: 0.158 AC: 4844 AN: 30590

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3361 AN: 21414

East Asian (EAS) AF: 0.224 AC: 7689 AN: 34348

South Asian (SAS) AF: 0.246 AC: 16503 AN: 67142

European-Finnish (FIN) AF: 0.137 AC: 6187 AN: 45288

Middle Eastern (MID) AF: 0.210 AC: 728 AN: 3468

European-Non Finnish (NFE) AF: 0.151 AC: 119173 AN: 789246

Other (OTH) AF: 0.204 AC: 9461 AN: 46456

GnomAD4 genome AF: 0.302 AC: 45983 AN: 152132 Hom.: 10539 Cov.: 33 AF XY: 0.298 AC XY: 22152 AN XY: 74394

African (AFR) AF: 0.645 AC: 26743 AN: 41462

American (AMR) AF: 0.205 AC: 3132 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5182

South Asian (SAS) AF: 0.252 AC: 1214 AN: 4812

European-Finnish (FIN) AF: 0.132 AC: 1402 AN: 10610

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10849 AN: 67986

Other (OTH) AF: 0.282 AC: 595 AN: 2110

Alfa AF: 0.186 Hom.: 5979

Bravo AF: 0.322

Asia WGS AF: 0.318 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.55
PhyloP100		2.4
PromoterAI		0.010	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3734744;

hg19: chr6-132696016;

COSMIC: COSV107411076;