Genetic Variant NM_001142651.3:c.481G>T (chr5-172670234-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142651.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEURL1B	NM_001142651.3	MANE Select	c.481G>T	p.Gly161Cys	missense	Exon 2 of 5	NP_001136123.1	A8MQ27-1
NEURL1B	NM_001308178.2		c.481G>T	p.Gly161Cys	missense	Exon 2 of 4	NP_001295107.1	A8MQ27-3
NEURL1B	NM_001308177.2		c.32-13185G>T		intron	N/A	NP_001295106.1	A8MQ27-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEURL1B	ENST00000369800.6	TSL:1 MANE Select	c.481G>T	p.Gly161Cys	missense	Exon 2 of 5	ENSP00000358815.5	A8MQ27-1
NEURL1B	ENST00000520919.5	TSL:1	c.481G>T	p.Gly161Cys	missense	Exon 2 of 4	ENSP00000429797.1	A8MQ27-3
NEURL1B	ENST00000522853.5	TSL:1	c.32-13185G>T		intron	N/A	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

African (AFR)

AF:

0.00

AC:

AN:

24878

American (AMR)

AF:

0.00

AC:

AN:

15722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19222

East Asian (EAS)

AF:

0.00

AC:

AN:

28636

South Asian (SAS)

AF:

0.00

AC:

AN:

61110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1018562

Other (OTH)

AF:

0.00

AC:

AN:

52304

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.033

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

PhyloP100

8.1

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.31

Sift

Benign

0.061

Sift4G

Uncertain

0.045

Polyphen

1.0

Vest4

0.28

MutPred

0.56

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

Mutation Taster

=59/41

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over