NM_001091.4:c.503A>C

Variant names:

• chr7-150856973-A-C
• NM_001091.4:c.503A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001091.4(AOC1):​c.503A>C​(p.Asn168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

Genes affected

AOC1 (HGNC:80): (amine oxidase copper containing 1) This gene encodes a metal-binding membrane glycoprotein that oxidatively deaminates putrescine, histamine, and related compounds. The encoded protein is inhibited by amiloride, a diuretic that acts by closing epithelial sodium ion channels. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

ENSG00000289052 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16754717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001091.4. 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
	AOC1	NM_001091.4	MANE Select	c.503A>C	p.Asn168Thr	missense	Exon 2 of 5	NP_001082.2	P19801-1
	AOC1	NM_001272072.2		c.503A>C	p.Asn168Thr	missense	Exon 2 of 5	NP_001259001.1	P19801-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC1	ENST00000360937.9	TSL:1 MANE Select	c.503A>C	p.Asn168Thr	missense	Exon 2 of 5	ENSP00000354193.4	P19801-1
	AOC1	ENST00000416793.6	TSL:1	c.503A>C	p.Asn168Thr	missense	Exon 2 of 5	ENSP00000411613.2	P19801-2
	AOC1	ENST00000941409.1		c.503A>C	p.Asn168Thr	missense	Exon 3 of 6	ENSP00000611468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.76	N
PhyloP100		2.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Uncertain	0.029	D
Sift4G	Benign	0.22	T
Polyphen		0.056	B
Vest4		0.20
MutPred		0.42		Loss of helix (P = 0.0167)
MVP		0.18
MPC		0.23
ClinPred		0.22	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.58
Mutation Taster		=74/26	polymorphism

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

hg19: chr7-150554061;