rs3797799

Variant names:

• chr5-96979374-T-A
• NM_005575.3:c.256T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-96979374-T-A
• chr5-96979374-T-C

Variant summary

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

The NM_005575.3(LNPEP):​c.256T>A​(p.Ser86Thr) 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. 13/21 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. S86P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LNPEP NM_005575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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

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=0.12404549).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.256T>A	p.Ser86Thr	missense_variant	Exon 2 of 18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.214T>A	p.Ser72Thr	missense_variant	Exon 2 of 18		NP_787116.2
LNPEP	XM_047417177.1	c.256T>A	p.Ser86Thr	missense_variant	Exon 2 of 16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.256T>A	p.Ser86Thr	missense_variant	Exon 2 of 18	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.214T>A	p.Ser72Thr	missense_variant	Exon 2 of 18	1		ENSP00000379117.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.0041
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.18
Sift	Benign	0.14	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.36	B;.
Vest4		0.17
MutPred		0.17		Gain of relative solvent accessibility (P = 0.09);.;
MVP		0.28
MPC		0.17
ClinPred		0.27	T
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.32

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: chr5-96315078;