chr5-97003542-A-T

Variant names:

• chr5-97003542-A-T
• rs12520455
• NM_005575.3:c.1781A>T

Variant summary

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

The NM_005575.3(LNPEP):​c.1781A>T​(p.Asn594Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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: not found (cov: 31)
• Consequence: LNPEP NM_005575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 4 publications found

Genes affected

LNPEP (HGNC:6656): (leucyl and cystinyl aminopeptidase) This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005575.3. 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
	LNPEP	NM_005575.3	MANE Select	c.1781A>T	p.Asn594Ile	missense	Exon 9 of 18	NP_005566.2	Q9UIQ6-1
	LNPEP	NM_175920.4		c.1739A>T	p.Asn580Ile	missense	Exon 9 of 18	NP_787116.2	Q9UIQ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	ENST00000231368.10	TSL:1 MANE Select	c.1781A>T	p.Asn594Ile	missense	Exon 9 of 18	ENSP00000231368.5	Q9UIQ6-1
	LNPEP	ENST00000395770.3	TSL:1	c.1739A>T	p.Asn580Ile	missense	Exon 9 of 18	ENSP00000379117.3	Q9UIQ6-2
	LNPEP	ENST00000930837.1		c.1778A>T	p.Asn593Ile	missense	Exon 9 of 18	ENSP00000600896.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.074
Sift	Benign	0.073	T
Sift4G	Benign	0.066	T
Polyphen		0.015	B
Vest4		0.87
MutPred		0.20		Loss of disorder (P = 0.1268)
MVP		0.17
MPC		0.67
ClinPred		0.79	D
GERP RS		4.6
Varity_R		0.35
gMVP		0.56
Mutation Taster		=58/42	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

dbSNP: rs12520455; hg19: chr5-96339246;