10-69572473-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020999.4(NEUROG3):​c.571C>G​(p.Arg191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R191Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

NEUROG3
NM_020999.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.329

Publications

0 publications found
Variant links:
Genes affected
NEUROG3 (HGNC:13806): (neurogenin 3) The protein encoded by this gene is a basic helix-loop-helix (bHLH) transcription factor involved in neurogenesis. The encoded protein likely acts as a heterodimer with another bHLH protein. Defects in this gene are a cause of congenital malabsorptive diarrhea 4 (DIAR4).[provided by RefSeq, May 2010]
NEUROG3 Gene-Disease associations (from GenCC):
  • congenital malabsorptive diarrhea 4
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • permanent neonatal diabetes mellitus
    Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04471764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEUROG3NM_020999.4 linkc.571C>G p.Arg191Gly missense_variant Exon 2 of 2 ENST00000242462.5 NP_066279.2 Q9Y4Z2
NEUROG3XM_017016280.2 linkc.571C>G p.Arg191Gly missense_variant Exon 2 of 2 XP_016871769.1 Q9Y4Z2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEUROG3ENST00000242462.5 linkc.571C>G p.Arg191Gly missense_variant Exon 2 of 2 1 NM_020999.4 ENSP00000242462.4 Q9Y4Z2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1437476
Hom.:
0
Cov.:
37
AF XY:
0.00
AC XY:
0
AN XY:
713528
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32772
American (AMR)
AF:
0.00
AC:
0
AN:
41232
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25748
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83876
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49698
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5576
European-Non Finnish (NFE)
AF:
9.08e-7
AC:
1
AN:
1101038
Other (OTH)
AF:
0.00
AC:
0
AN:
59344
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
3.0
DANN
Benign
0.89
DEOGEN2
Benign
0.16
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.070
D
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
0.81
L
PhyloP100
0.33
PrimateAI
Benign
0.45
T
PROVEAN
Benign
0.37
N
REVEL
Benign
0.19
Sift
Benign
0.54
T
Sift4G
Benign
0.40
T
Polyphen
0.0
B
Vest4
0.039
MutPred
0.31
Loss of stability (P = 0.0465);
MVP
0.72
MPC
0.52
ClinPred
0.11
T
GERP RS
-1.4
Varity_R
0.059
gMVP
0.71
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs770935946; hg19: chr10-71332229; API