chr10-69572485-A-T

Variant names:

Variant summary

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

The NM_020999.4(NEUROG3):c.559T>A(p.Ser187Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000181 in 1,436,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

NEUROG3
NM_020999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

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:

Genome browser will be placed here

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=0.26212823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROG3	NM_020999.4 link	c.559T>A	p.Ser187Thr	missense_variant	Exon 2 of 2	ENST00000242462.5	NP_066279.2	Q9Y4Z2
NEUROG3	XM_017016280.2 link	c.559T>A	p.Ser187Thr	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.559T>A	p.Ser187Thr	missense_variant	Exon 2 of 2	1	NM_020999.4	ENSP00000242462.4		Q9Y4Z2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000507

AC:

AN:

197354

AF XY:

0.00000921

show subpopulations

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:

0.0000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000181

AC:

AN:

1436524

Hom.:

Cov.:

AF XY:

0.0000210

AC XY:

AN XY:

712944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32724

American (AMR)

AF:

0.00

AC:

AN:

40854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25718

East Asian (EAS)

AF:

0.00

AC:

AN:

38006

South Asian (SAS)

AF:

0.00

AC:

AN:

83842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.0000218

AC:

AN:

1100256

Other (OTH)

AF:

0.0000337

AC:

AN:

59312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.559T>A (p.S187T) alteration is located in exon 2 (coding exon 1) of the NEUROG3 gene. This alteration results from a T to A substitution at nucleotide position 559, causing the serine (S) at amino acid position 187 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

0.10

BayesDel_addAF

Benign

0.0044

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Benign

0.011

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.50

M_CAP

Benign

0.081

MetaRNN

Benign

0.26

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

1.1

PhyloP100

3.8

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.93

REVEL

Benign

0.26

Sift

Benign

0.075

Sift4G

Uncertain

0.039

Polyphen

0.47

Vest4

0.29

MutPred

0.25

Gain of glycosylation at S187 (P = 0.0477);

MVP

0.98

MPC

1.2

ClinPred

0.77

GERP RS

4.7

Varity_R

0.18

gMVP

0.74

Mutation Taster

=91/9

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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chr10-69572485-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over