17-7317858-C-T

Variant summary

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

The NM_032442.3(NEURL4):​c.4135G>A​(p.Ala1379Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

NEURL4
NM_032442.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
Variant links:
Genes affected
NEURL4 (HGNC:34410): (neuralized E3 ubiquitin protein ligase 4) The protein encoded by this gene is predicted and it includes two isoforms resulting from two alternatively spliced transcript variants. [provided by RefSeq, Jul 2008]

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=0.114259034).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEURL4NM_032442.3 linkc.4135G>A p.Ala1379Thr missense_variant Exon 26 of 29 ENST00000399464.7 NP_115818.2 Q96JN8-1
NEURL4NM_001005408.2 linkc.4129G>A p.Ala1377Thr missense_variant Exon 26 of 29 NP_001005408.1 Q96JN8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEURL4ENST00000399464.7 linkc.4135G>A p.Ala1379Thr missense_variant Exon 26 of 29 1 NM_032442.3 ENSP00000382390.2 Q96JN8-1
ENSG00000261915ENST00000575474.1 linkn.574G>A non_coding_transcript_exon_variant Exon 5 of 19 5 ENSP00000468772.1 K7ESM1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4135G>A (p.A1379T) alteration is located in exon 26 (coding exon 26) of the NEURL4 gene. This alteration results from a G to A substitution at nucleotide position 4135, causing the alanine (A) at amino acid position 1379 to be replaced by a threonine (T). 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
0.092
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Benign
0.93
DEOGEN2
Benign
0.0083
.;T;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.63
.;N;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.87
N;N;.
REVEL
Benign
0.080
Sift
Benign
0.47
T;T;.
Sift4G
Benign
0.43
T;T;T
Polyphen
0.035
B;B;.
Vest4
0.38
MutPred
0.13
.;Gain of phosphorylation at A1379 (P = 0.0098);.;
MVP
0.082
MPC
0.68
ClinPred
0.62
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.082
gMVP
0.63

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: rs2072971554; hg19: chr17-7221177; API