5-65785782-C-G

Position:

• chr5-65785782-C-G

Variant summary

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

The ENST00000380985.10(NLN):​c.830C>G​(p.Thr277Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLN ENST00000380985.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68

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]

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=0.17680329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLN	NM_020726.5	c.830C>G	p.Thr277Ser	missense_variant	7/13	ENST00000380985.10	NP_065777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLN	ENST00000380985.10	c.830C>G	p.Thr277Ser	missense_variant	7/13	1	NM_020726.5	ENSP00000370372	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.830C>G (p.T277S) alteration is located in exon 7 (coding exon 7) of the NLN gene. This alteration results from a C to G substitution at nucleotide position 830, causing the threonine (T) at amino acid position 277 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.51	N;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.29	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0050	B;.;.
Vest4		0.36
MutPred		0.47		Loss of ubiquitination at K273 (P = 0.1372);.;.;
MVP		0.34
MPC		0.10
ClinPred		0.53	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-65081609;