15-89797719-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001150.3(ANPEP):c.2013C>G(p.Ala671=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,614,004 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (68 hom.)
• Consequence: ANPEP NM_001150.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.44

Genes affected

ANPEP (HGNC:500): (alanyl aminopeptidase, membrane) Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-89797719-G-C is Benign according to our data. Variant chr15-89797719-G-C is described in ClinVar as [Benign]. Clinvar id is 720704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.44 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANPEP	NM_001150.3	c.2013C>G	p.Ala671=	synonymous_variant	15/21	ENST00000300060.7
ANPEP	NM_001381923.1	c.2013C>G	p.Ala671=	synonymous_variant	15/21
ANPEP	NM_001381924.1	c.2013C>G	p.Ala671=	synonymous_variant	14/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANPEP	ENST00000300060.7	c.2013C>G	p.Ala671=	synonymous_variant	15/21	1	NM_001150.3	P1

Frequencies

GnomAD3 genomes AF: 0.00650 AC: 989 AN: 152110 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00707 AC: 1776 AN: 251296 Hom.: 9 AF XY: 0.00724 AC XY: 983 AN XY: 135826

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.0186

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00127

Gnomad FIN exome AF: 0.00790

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00962

GnomAD4 exome AF: 0.00825 AC: 12055 AN: 1461776 Hom.: 68 Cov.: 31 AF XY: 0.00818 AC XY: 5949 AN XY: 727186

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00138

Gnomad4 FIN exome AF: 0.00844

Gnomad4 NFE exome AF: 0.00928

Gnomad4 OTH exome AF: 0.00734

GnomAD4 genome AF: 0.00650 AC: 989 AN: 152228 Hom.: 4 Cov.: 32 AF XY: 0.00632 AC XY: 470 AN XY: 74426

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.00963

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00922 Hom.: 3

Bravo AF: 0.00594

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.00954

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.95
Dann	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs150492701; hg19: chr15-90340950; COSMIC: COSV55595932; COSMIC: COSV55595932;