10-103571714-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004210.5(NEURL1):​c.541C>T​(p.Arg181Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

NEURL1
NM_004210.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17946857).
BS2
High AC in GnomAdExome4 at 56 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEURL1NM_004210.5 linkc.541C>T p.Arg181Cys missense_variant Exon 3 of 6 ENST00000369780.9 NP_004201.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEURL1ENST00000369780.9 linkc.541C>T p.Arg181Cys missense_variant Exon 3 of 6 1 NM_004210.5 ENSP00000358795.4 O76050-1
NEURL1ENST00000437579.1 linkc.490C>T p.Arg164Cys missense_variant Exon 3 of 3 2 ENSP00000416709.1 X6RLA8
NEURL1ENST00000455386.1 linkc.316C>T p.Arg106Cys missense_variant Exon 3 of 3 2 ENSP00000387714.1 X6RBV8
NEURL1ENST00000465048.1 linkn.38C>T non_coding_transcript_exon_variant Exon 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152266
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251364
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1461844
Hom.:
0
Cov.:
32
AF XY:
0.0000344
AC XY:
25
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
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:
0.0000423
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152266
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.541C>T (p.R181C) alteration is located in exon 3 (coding exon 3) of the NEURL1 gene. This alteration results from a C to T substitution at nucleotide position 541, causing the arginine (R) at amino acid position 181 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
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.42
T;.;.
Eigen
Benign
-0.077
Eigen_PC
Benign
0.062
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Benign
0.17
Sift
Benign
0.13
T;T;T
Sift4G
Benign
0.068
T;T;T
Polyphen
0.042
B;.;.
Vest4
0.52
MVP
0.48
MPC
1.1
ClinPred
0.24
T
GERP RS
4.7
Varity_R
0.32
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs764248097; hg19: chr10-105331471; API