Genetic Variant NEUROG3:p.Thr198Thr (chr10-69572450-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_020999.4(NEUROG3):c.594C>G(p.Thr198Thr) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T198T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEUROG3
NM_020999.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.471

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet
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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-69572450-G-C is Benign according to our data. Variant chr10-69572450-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3647060.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.471 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020999.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG3	NM_020999.4	MANE Select	c.594C>G	p.Thr198Thr	synonymous	Exon 2 of 2	NP_066279.2	Q9Y4Z2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEUROG3	ENST00000242462.5	TSL:1 MANE Select	c.594C>G	p.Thr198Thr	synonymous	Exon 2 of 2	ENSP00000242462.4	Q9Y4Z2
NEUROG3	ENST00000929784.1		c.594C>G	p.Thr198Thr	synonymous	Exon 2 of 2	ENSP00000599843.1
ENSG00000236154	ENST00000839697.1		n.340G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713678

African (AFR)

AF:

0.00

AC:

AN:

32844

American (AMR)

AF:

0.00

AC:

AN:

41870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25764

East Asian (EAS)

AF:

0.00

AC:

AN:

38496

South Asian (SAS)

AF:

0.00

AC:

AN:

83966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102078

Other (OTH)

AF:

0.00

AC:

AN:

59452

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.54

PhyloP100

-0.47

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over