Variant 5-135535542-C-T 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.149G>A(p.Arg50Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000493 in 1,420,596 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: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

NEUROG1
NM_006161.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.647

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=0.1888228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEUROG1	NM_006161.3 linkuse as main transcript	c.149G>A	p.Arg50Lys	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.149G>A	p.Arg50Lys	missense_variant	1/1	6	NM_006161.3	ENSP00000317580.4	Q92886
ENSG00000250167	ENST00000698884.1 linkuse as main transcript	n.496+48773C>T		intron_variant
SLC25A48	ENST00000698885.1 linkuse as main transcript	n.364+25786C>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000222

AC:

AN:

180368

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

100148

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 SAS exome

AF:

0.000156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000493

AC:

AN:

1420596

Hom.:

Cov.:

AF XY:

0.00000851

AC XY:

AN XY:

704690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000852

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000172

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

Mar 25, 2024

The c.149G>A (p.R50K) alteration is located in exon 1 (coding exon 1) of the NEUROG1 gene. This alteration results from a G to A substitution at nucleotide position 149, causing the arginine (R) at amino acid position 50 to be replaced by a lysine (K). 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

-0.19

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.28

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.37

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.19

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.35

REVEL

Benign

0.26

Sift

Benign

0.14

Sift4G

Benign

0.97

Polyphen

0.63

Vest4

0.052

MutPred

0.35

Gain of ubiquitination at R50 (P = 0.0077);

MVP

0.83

MPC

0.49

ClinPred

0.064

GERP RS

4.2

Varity_R

0.16

gMVP

0.46

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