7-150860577-C-T

Position:

• chr7-150860577-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001091.4(AOC1):​c.1933C>T​(p.His645Tyr) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H645D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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]

AOC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124961585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOC1	NM_001091.4	c.1933C>T	p.His645Tyr	missense_variant	4/5	ENST00000360937.9	NP_001082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9	c.1933C>T	p.His645Tyr	missense_variant	4/5	1	NM_001091.4	ENSP00000354193.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T;T;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.50	.;T;.;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;N;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.092
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.50	P;P;P;.
Vest4		0.15
MutPred		0.27		Loss of disorder (P = 0.0531);Loss of disorder (P = 0.0531);Loss of disorder (P = 0.0531);.;
MVP		0.10
MPC		0.39
ClinPred		0.76	D
GERP RS		3.1
Varity_R		0.25
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1049793; hg19: chr7-150557665;