Variant 5-65758758-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020726.5(NLN):c.233T>G(p.Leu78Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NLN
NM_020726.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

Variant links:

Genes affected

NLN (HGNC:16058): (neurolysin) This gene encodes a member of the metallopeptidase M3 protein family that cleaves neurotensin at the Pro10-Tyr11 bond, leading to the formation of neurotensin(1-10) and neurotensin(11-13). The encoded protein is likely involved in the termination of the neurotensinergic signal in the central nervous system and in the gastrointestinal tract.[provided by RefSeq, Jun 2010]

NLN links:

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ACMG classification

Classification made for transcript

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
NLN	NM_020726.5 linkuse as main transcript	c.233T>G	p.Leu78Arg	missense_variant	2/13	ENST00000380985.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NLN	ENST00000380985.10 linkuse as main transcript	c.233T>G	p.Leu78Arg	missense_variant	2/13	1	NM_020726.5	P1
NLN	ENST00000506539.5 linkuse as main transcript	n.349T>G		non_coding_transcript_exon_variant	2/9	1
NLN	ENST00000502464.5 linkuse as main transcript	c.-11-4202T>G		intron_variant		5
NLN	ENST00000514991.5 linkuse as main transcript	c.*192T>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251266

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.233T>G (p.L78R) alteration is located in exon 2 (coding exon 2) of the NLN gene. This alteration results from a T to G substitution at nucleotide position 233, causing the leucine (L) at amino acid position 78 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.63

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.15

Sift

Uncertain

0.023

Sift4G

Uncertain

0.011

Polyphen

0.0080

Vest4

0.54

MutPred

0.49

Gain of solvent accessibility (P = 0.0155);

MVP

0.28

MPC

0.18

ClinPred

0.90

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.50

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over