Variant 5-135535143-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006161.3(NEUROG1):c.548C>G(p.Ala183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,608,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

NEUROG1
NM_006161.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

NEUROG1 (HGNC:7764): (neurogenin 1) Enables E-box binding activity and protein homodimerization activity. Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. Predicted to be located in neuronal cell body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NEUROG1 links:

ENSG00000250167 (HGNC:):

ENSG00000250167 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09651011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEUROG1	NM_006161.3 linkuse as main transcript	c.548C>G	p.Ala183Gly	missense_variant	1/1	ENST00000314744.6	NP_006152.2	Q92886F1T0H3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEUROG1	ENST00000314744.6 linkuse as main transcript	c.548C>G	p.Ala183Gly	missense_variant	1/1	6	NM_006161.3	ENSP00000317580.4	Q92886
ENSG00000250167	ENST00000698884.1 linkuse as main transcript	n.496+48374G>C		intron_variant
SLC25A48	ENST00000698885.1 linkuse as main transcript	n.364+25387G>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000160

AC:

AN:

237500

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

129550

show subpopulations

Gnomad AFR exome

AF:

0.0000694

Gnomad AMR exome

AF:

0.000736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000517

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1456822

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

724384

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.000743

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.000158

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000428

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.548C>G (p.A183G) alteration is located in exon 1 (coding exon 1) of the NEUROG1 gene. This alteration results from a C to G substitution at nucleotide position 548, causing the alanine (A) at amino acid position 183 to be replaced by a glycine (G). 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

0.090

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.29

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.097

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.0

REVEL

Benign

0.24

Sift

Benign

0.28

Sift4G

Benign

0.24

Polyphen

0.0040

Vest4

0.063

MutPred

0.15

Gain of catalytic residue at P179 (P = 0.0973);

MVP

0.65

MPC

0.58

ClinPred

0.017

GERP RS

3.1

Varity_R

0.086

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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