Genetic Variant NEUROG1:p.Glu162Lys (chr5-135535207-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006161.3(NEUROG1):c.484G>A(p.Glu162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000565 in 1,611,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

NEUROG1
NM_006161.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Publications

0 publications found

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:

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A48 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3416894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006161.3. 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
	NEUROG1	NM_006161.3	MANE Select	c.484G>A	p.Glu162Lys	missense	Exon 1 of 1	NP_006152.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEUROG1	ENST00000314744.6	TSL:6 MANE Select	c.484G>A	p.Glu162Lys	missense	Exon 1 of 1	ENSP00000317580.4	Q92886
ENSG00000250167	ENST00000698884.1		n.496+48438C>T		intron	N/A
SLC25A48	ENST00000698885.1		n.364+25451C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000416

AC:

AN:

240338

AF XY:

0.0000532

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:

0.0000844

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000562

AC:

AN:

1458832

Hom.:

Cov.:

AF XY:

0.0000661

AC XY:

AN XY:

725692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

86156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.0000630

AC:

AN:

1110932

Other (OTH)

AF:

0.000199

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.4

PhyloP100

1.3

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.69

REVEL

Benign

0.28

Sift

Benign

0.12

Sift4G

Benign

0.41

Polyphen

0.068

Vest4

0.16

MutPred

0.40

Gain of ubiquitination at E162 (P = 0.0146)

MVP

0.90

MPC

0.57

ClinPred

0.12

GERP RS

5.0

Varity_R

0.14

gMVP

0.76

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over