NM_006161.3:c.548C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006161.3(NEUROG1):c.548C>A(p.Ala183Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,609,062 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A183V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0045 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 9 hom. )

Consequence

NEUROG1
NM_006161.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.74

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005898416).

BP6

Variant 5-135535143-G-T is Benign according to our data. Variant chr5-135535143-G-T is described in ClinVar as Benign. ClinVar VariationId is 721273.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

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.548C>A	p.Ala183Glu	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.548C>A	p.Ala183Glu	missense	Exon 1 of 1	ENSP00000317580.4	Q92886
ENSG00000250167	ENST00000698884.1		n.496+48374G>T		intron	N/A
SLC25A48	ENST00000698885.1		n.364+25387G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

684

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00127

AC:

301

AN:

237500

AF XY:

0.000965

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.000883

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000861

GnomAD4 exome

AF:

0.000502

AC:

732

AN:

1456822

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

326

AN XY:

724384

show subpopulations

African (AFR)

AF:

0.0160

AC:

531

AN:

33222

American (AMR)

AF:

0.000946

AC:

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25762

East Asian (EAS)

AF:

0.00

AC:

AN:

39592

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52906

Middle Eastern (MID)

AF:

0.000363

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

0.0000775

AC:

AN:

1109732

Other (OTH)

AF:

0.00116

AC:

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

131

175

219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00451

AC:

687

AN:

152240

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0159

AC:

660

AN:

41548

American (AMR)

AF:

0.00137

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68008

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000539

Hom.:

Bravo

AF:

0.00535

ESP6500AA

AF:

0.0167

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00142

AC:

171

ClinVar

ClinVar submissions

Significance: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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Uncertain

0.52

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0059

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.8

PhyloP100

1.7

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.9

REVEL

Benign

0.23

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.036

Polyphen

0.81

Vest4

0.30

MVP

0.75

MPC

0.75

ClinPred

0.014

GERP RS

3.1

Varity_R

0.22

gMVP

0.73

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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