10-69572448-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020999.4(NEUROG3):c.596T>C(p.Phe199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,586,694 control chromosomes in the GnomAD database, including 319,244 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24507 hom., cov: 33)

Exomes 𝑓: 0.63 ( 294737 hom. )

Consequence

NEUROG3
NM_020999.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.90

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0075619E-5).

BP6

Variant 10-69572448-A-G is Benign according to our data. Variant chr10-69572448-A-G is described in ClinVar as [Benign]. Clinvar id is 129765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEUROG3	NM_020999.4 link	c.596T>C	p.Phe199Ser	missense_variant	Exon 2 of 2	ENST00000242462.5	NP_066279.2	Q9Y4Z2
NEUROG3	XM_017016280.2 link	c.596T>C	p.Phe199Ser	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.596T>C	p.Phe199Ser	missense_variant	Exon 2 of 2	1	NM_020999.4	ENSP00000242462.4		Q9Y4Z2

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83069

AN:

151906

Hom.:

24504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.672

Gnomad OTH

AF:

0.544

GnomAD3 exomes

AF:

0.561

AC:

113541

AN:

202444

Hom.:

33227

AF XY:

0.561

AC XY:

62600

AN XY:

111680

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.552

Gnomad EAS exome

AF:

0.310

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.633

AC:

908369

AN:

1434668

Hom.:

294737

Cov.:

AF XY:

0.628

AC XY:

447487

AN XY:

712452

show subpopulations

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.581

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.302

Gnomad4 SAS exome

AF:

0.458

Gnomad4 FIN exome

AF:

0.646

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.547

AC:

83090

AN:

152026

Hom.:

24507

Cov.:

AF XY:

0.544

AC XY:

40395

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.614

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.442

Gnomad4 FIN

AF:

0.641

Gnomad4 NFE

AF:

0.672

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.630

Hom.:

59456

Bravo

AF:

0.531

TwinsUK

AF:

0.672

AC:

2493

ALSPAC

AF:

0.671

AC:

2585

ESP6500AA

AF:

0.395

AC:

1453

ESP6500EA

AF:

0.679

AC:

5305

ExAC

AF:

0.534

AC:

62528

Asia WGS

AF:

0.404

AC:

1408

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 11206403, 17146417) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Congenital malabsorptive diarrhea 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.14

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.14

MetaRNN

Benign

0.000010

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

1.5

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.028

MPC

0.72

ClinPred

0.0014

GERP RS

2.9

Varity_R

0.052

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over