Genetic Variant NEUROG3:p.Cys202Tyr (chr10-69572439-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020999.4(NEUROG3):c.605G>A(p.Cys202Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. C202F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEUROG3
NM_020999.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.137

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

NEUROG3 links:

ENSG00000236154 (HGNC:):

ENSG00000236154 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09887475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROG3	NM_020999.4 link	c.605G>A	p.Cys202Tyr	missense_variant	Exon 2 of 2	ENST00000242462.5	NP_066279.2	Q9Y4Z2
NEUROG3	XM_017016280.2 link	c.605G>A	p.Cys202Tyr	missense_variant	Exon 2 of 2		XP_016871769.1	Q9Y4Z2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEUROG3	ENST00000242462.5 link	c.605G>A	p.Cys202Tyr	missense_variant	Exon 2 of 2	1	NM_020999.4	ENSP00000242462.4		Q9Y4Z2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

203290

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713964

African (AFR)

AF:

0.00

AC:

AN:

32882

American (AMR)

AF:

0.00

AC:

AN:

42372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25796

East Asian (EAS)

AF:

0.00

AC:

AN:

38624

South Asian (SAS)

AF:

0.00

AC:

AN:

84134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103188

Other (OTH)

AF:

0.00

AC:

AN:

59568

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

6.6

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.23

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.28

M_CAP

Benign

0.032

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.63

PhyloP100

0.14

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.99

REVEL

Benign

0.18

Sift

Benign

0.11

Sift4G

Benign

0.22

Polyphen

0.0020

Vest4

0.094

MutPred

0.25

Gain of phosphorylation at C202 (P = 0.1076);

MVP

0.85

MPC

0.69

ClinPred

0.077

GERP RS

0.51

Varity_R

0.095

gMVP

0.64

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over