17-7316233-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032442.3(NEURL4):​c.4579G>A​(p.Ala1527Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,613,772 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 3 hom. )

Consequence

NEURL4
NM_032442.3 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.705
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0034599602).
BP6
Variant 17-7316233-C-T is Benign according to our data. Variant chr17-7316233-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3390331.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEURL4NM_032442.3 linkc.4579G>A p.Ala1527Thr missense_variant Exon 29 of 29 ENST00000399464.7 NP_115818.2 Q96JN8-1
NEURL4NM_001005408.2 linkc.4573G>A p.Ala1525Thr missense_variant Exon 29 of 29 NP_001005408.1 Q96JN8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEURL4ENST00000399464.7 linkc.4579G>A p.Ala1527Thr missense_variant Exon 29 of 29 1 NM_032442.3 ENSP00000382390.2 Q96JN8-1
ENSG00000261915ENST00000575474.1 linkn.975+43G>A intron_variant Intron 8 of 18 5 ENSP00000468772.1 K7ESM1

Frequencies

GnomAD3 genomes
AF:
0.000914
AC:
139
AN:
152138
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00971
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000456
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00114
AC:
284
AN:
249484
Hom.:
2
AF XY:
0.00116
AC XY:
157
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00119
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00951
Gnomad NFE exome
AF:
0.000512
Gnomad OTH exome
AF:
0.000825
GnomAD4 exome
AF:
0.000629
AC:
919
AN:
1461516
Hom.:
3
Cov.:
31
AF XY:
0.000612
AC XY:
445
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00871
Gnomad4 NFE exome
AF:
0.000347
Gnomad4 OTH exome
AF:
0.000547
GnomAD4 genome
AF:
0.000913
AC:
139
AN:
152256
Hom.:
1
Cov.:
32
AF XY:
0.00138
AC XY:
103
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00971
Gnomad4 NFE
AF:
0.000456
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000477
Hom.:
0
Bravo
AF:
0.000185
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000481
AC:
4
ExAC
AF:
0.000976
AC:
118
EpiCase
AF:
0.000763
EpiControl
AF:
0.000474

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

NEURL4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0085
.;T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.0035
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.89
.;L;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.90
N;N;.
REVEL
Benign
0.036
Sift
Benign
0.21
T;T;.
Sift4G
Benign
0.30
T;T;T
Polyphen
0.0070
B;B;.
Vest4
0.042
MVP
0.043
MPC
0.51
ClinPred
0.023
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.082
gMVP
0.23

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: rs201366443; hg19: chr17-7219552; API