Variant chr5-172670234-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001142651.3(NEURL1B):c.481G>T(p.Gly161Cys) variant causes a missense change involving the alteration of a 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEURL1B
NM_001142651.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.12

Variant links:

Genes affected

NEURL1B (HGNC:35422): (neuralized E3 ubiquitin protein ligase 1B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent endocytosis. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NEURL1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29391277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NEURL1B	NM_001142651.3 linkuse as main transcript	c.481G>T	p.Gly161Cys	missense_variant	2/5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308178.2 linkuse as main transcript	c.481G>T	p.Gly161Cys	missense_variant	2/4		NP_001295107.1
NEURL1B	NM_001308177.2 linkuse as main transcript	c.32-13185G>T		intron_variant			NP_001295106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEURL1B	ENST00000369800.6 linkuse as main transcript	c.481G>T	p.Gly161Cys	missense_variant	2/5	1	NM_001142651.3	ENSP00000358815.5	A8MQ27-1
NEURL1B	ENST00000520919.5 linkuse as main transcript	c.481G>T	p.Gly161Cys	missense_variant	2/4	1		ENSP00000429797.1	A8MQ27-3
NEURL1B	ENST00000522853.5 linkuse as main transcript	c.32-13185G>T		intron_variant		1		ENSP00000430001.1	A8MQ27-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1259682

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

611324

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

Sep 14, 2023

The c.481G>T (p.G161C) alteration is located in exon 2 (coding exon 2) of the NEURL1B gene. This alteration results from a G to T substitution at nucleotide position 481, causing the glycine (G) at amino acid position 161 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.31

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.045

D;T

Polyphen

1.0

.;D

Vest4

0.28

MutPred

0.56

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.48

MPC

1.4

ClinPred

0.99

GERP RS

5.5

Varity_R

0.43

gMVP

0.66

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