Variant 1-71776283-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173808.3(NEGR1):c.424T>C(p.Tyr142His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEGR1
NM_173808.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

NEGR1 (HGNC:17302): (neuronal growth regulator 1) Predicted to act upstream of or within several processes, including feeding behavior; locomotory behavior; and positive regulation of neuron projection development. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEGR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23307389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEGR1	NM_173808.3 link	c.424T>C	p.Tyr142His	missense_variant	3/7	ENST00000357731.10	NP_776169.2	Q7Z3B1-1
NEGR1	XM_011541200.4 link	c.424T>C	p.Tyr142His	missense_variant	3/7		XP_011539502.1
NEGR1	XM_011541201.4 link	c.424T>C	p.Tyr142His	missense_variant	3/5		XP_011539503.1
NEGR1	XM_017000961.3 link	c.424T>C	p.Tyr142His	missense_variant	3/5		XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEGR1	ENST00000357731.10 link	c.424T>C	p.Tyr142His	missense_variant	3/7	1	NM_173808.3	ENSP00000350364.4	Q7Z3B1-1
NEGR1	ENST00000306821.3 link	c.40T>C	p.Tyr14His	missense_variant	3/7	1		ENSP00000305938.3	Q7Z3B1-2
NEGR1	ENST00000467479.1 link	n.421T>C		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717626

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:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Oct 17, 2024

The c.424T>C (p.Y142H) alteration is located in exon 3 (coding exon 3) of the NEGR1 gene. This alteration results from a T to C substitution at nucleotide position 424, causing the tyrosine (Y) at amino acid position 142 to be replaced by a histidine (H). 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

0.19

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.64

N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.017

D;T

Sift4G

Benign

0.16

T;T

Polyphen

0.95

P;.

Vest4

0.45

MutPred

0.49

Gain of disorder (P = 0.0251);.;

MVP

0.13

MPC

0.57

ClinPred

0.58

GERP RS

6.0

Varity_R

0.53

gMVP

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over