Variant 10-103571018-C-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_004210.5(NEURL1):c.232C>G(p.Leu78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NEURL1
NM_004210.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.698

Variant links:

Genes affected

NEURL1 (HGNC:7761): (neuralized E3 ubiquitin protein ligase 1) Predicted to enable translation factor activity, non-nucleic acid binding and ubiquitin protein ligase activity. Involved in negative regulation of Notch signaling pathway; negative regulation of cell population proliferation; and positive regulation of apoptotic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEURL1 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=0.23864833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEURL1	NM_004210.5 linkuse as main transcript	c.232C>G	p.Leu78Val	missense_variant	2/6	ENST00000369780.9	NP_004201.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEURL1	ENST00000369780.9 linkuse as main transcript	c.232C>G	p.Leu78Val	missense_variant	2/6	1	NM_004210.5	ENSP00000358795.4	O76050-1
NEURL1	ENST00000437579.1 linkuse as main transcript	c.181C>G	p.Leu61Val	missense_variant	2/3	2		ENSP00000416709.1	X6RLA8
NEURL1	ENST00000455386.1 linkuse as main transcript	c.7C>G	p.Leu3Val	missense_variant	2/3	2		ENSP00000387714.1	X6RBV8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250994

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0000617

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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

Nov 09, 2024

The c.232C>G (p.L78V) alteration is located in exon 2 (coding exon 2) of the NEURL1 gene. This alteration results from a C to G substitution at nucleotide position 232, causing the leucine (L) at amino acid position 78 to be replaced by a valine (V). 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

0.067

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.87

D;D;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.84

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.91

P;.;.

Vest4

0.18

MutPred

0.42

Gain of MoRF binding (P = 0.0887);.;.;

MVP

0.22

MPC

0.96

ClinPred

0.39

GERP RS

5.2

Varity_R

0.16

gMVP

0.22

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