rs10156191

Variant names:

• chr7-150856517-C-T
• rs10156191
• NM_001091.4:c.47C>T

Variant summary

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

The NM_001091.4(AOC1):​c.47C>T​(p.Thr16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,618 control chromosomes in the GnomAD database, including 62,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9422 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53086 hom.)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 66 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.31944E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC1	NM_001091.4	c.47C>T	p.Thr16Met	missense_variant	Exon 2 of 5	ENST00000360937.9	NP_001082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9	c.47C>T	p.Thr16Met	missense_variant	Exon 2 of 5	1	NM_001091.4	ENSP00000354193.4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49511 AN: 151884 Hom.: 9397 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.261 AC: 64895 AN: 248794 AF XY: 0.260

Gnomad AFR exome AF: 0.532

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.262 AC: 382663 AN: 1461616 Hom.: 53086 Cov.: 37 AF XY: 0.261 AC XY: 189675 AN XY: 727094

African (AFR) AF: 0.524 AC: 17544 AN: 33476

American (AMR) AF: 0.180 AC: 8034 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7334 AN: 26124

East Asian (EAS) AF: 0.114 AC: 4536 AN: 39700

South Asian (SAS) AF: 0.262 AC: 22589 AN: 86250

European-Finnish (FIN) AF: 0.289 AC: 15414 AN: 53346

Middle Eastern (MID) AF: 0.231 AC: 1330 AN: 5768

European-Non Finnish (NFE) AF: 0.261 AC: 290055 AN: 1111852

Other (OTH) AF: 0.262 AC: 15827 AN: 60390

GnomAD4 genome AF: 0.326 AC: 49577 AN: 152002 Hom.: 9422 Cov.: 32 AF XY: 0.323 AC XY: 24038 AN XY: 74318

African (AFR) AF: 0.520 AC: 21537 AN: 41452

American (AMR) AF: 0.229 AC: 3495 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3464

East Asian (EAS) AF: 0.123 AC: 635 AN: 5160

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4816

European-Finnish (FIN) AF: 0.282 AC: 2984 AN: 10588

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17660 AN: 67932

Other (OTH) AF: 0.283 AC: 597 AN: 2106

Alfa AF: 0.270 Hom.: 17788

Bravo AF: 0.331

TwinsUK AF: 0.257 AC: 953

ALSPAC AF: 0.250 AC: 962

ESP6500AA AF: 0.508 AC: 1966

ESP6500EA AF: 0.267 AC: 2203

ExAC AF: 0.270 AC: 32562

Asia WGS AF: 0.215 AC: 752 AN: 3478

EpiCase AF: 0.265

EpiControl AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.5
DANN	Benign	0.63
DEOGEN2	Benign	0.086	T;T;.;T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.23	.;T;T;.;T;T
MetaRNN	Benign	0.000033	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.84	N;N;.;N;N;.
PhyloP100		-0.13
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.36	N;N;N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.21	T;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.0010	B;B;.;B;.;.
Vest4		0.030
MPC		0.22
ClinPred		0.0019	T
GERP RS		-0.64
Varity_R		0.013
gMVP		0.22
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs10156191; hg19: chr7-150553605; COSMIC: COSV62868300; COSMIC: COSV62868300;