chr7-150857228-A-T

Position:

• chr7-150857228-A-T

Variant summary

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

The NM_001091.4(AOC1):​c.758A>T​(p.Tyr253Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.27

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]

LOC105375567 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOC1	NM_001091.4	c.758A>T	p.Tyr253Phe	missense_variant	2/5	ENST00000360937.9
LOC105375567	XR_928171.3	n.123-15783T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOC1	ENST00000360937.9	c.758A>T	p.Tyr253Phe	missense_variant	2/5	1	NM_001091.4	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.758A>T (p.Y253F) alteration is located in exon 2 (coding exon 1) of the AOC1 gene. This alteration results from a A to T substitution at nucleotide position 758, causing the tyrosine (Y) at amino acid position 253 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T;T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	.;D;.;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D;D;D;D;T
Sift4G	Benign	0.35	T;T;T;T;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.56
MutPred		0.60		Gain of methylation at K252 (P = 0.0267);Gain of methylation at K252 (P = 0.0267);Gain of methylation at K252 (P = 0.0267);Gain of methylation at K252 (P = 0.0267);Gain of methylation at K252 (P = 0.0267);
MVP		0.085
MPC		0.76
ClinPred		0.87	D
GERP RS		5.1
Varity_R		0.60
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150554316;