Genetic Variant NSG2:p.Pro165Leu (chr5-174107483-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015980.5(NSG2):c.494C>T(p.Pro165Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,609,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

NSG2
NM_015980.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

Publications

0 publications found

Variant links:

Genes affected

NSG2 (HGNC:24955): (neuronal vesicle trafficking associated 2) Predicted to enable clathrin light chain binding activity. Predicted to be involved in clathrin coat assembly and endosomal transport. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

NSG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074902177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015980.5. 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
	NSG2	NM_015980.5	MANE Select	c.494C>T	p.Pro165Leu	missense	Exon 5 of 5	NP_057064.1	Q9Y328

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NSG2	ENST00000303177.8	TSL:1 MANE Select	c.494C>T	p.Pro165Leu	missense	Exon 5 of 5	ENSP00000307722.3	Q9Y328
NSG2	ENST00000519717.1	TSL:1	c.494C>T	p.Pro165Leu	missense	Exon 4 of 4	ENSP00000431119.1	Q9Y328
NSG2	ENST00000892999.1		c.494C>T	p.Pro165Leu	missense	Exon 5 of 5	ENSP00000563058.1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00461

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:

0.00

GnomAD2 exomes

AF:

0.000321

AC:

AN:

246342

AF XY:

0.000291

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000811

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000182

AC:

265

AN:

1457394

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

123

AN XY:

724100

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33406

American (AMR)

AF:

0.000225

AC:

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.00599

AC:

156

AN:

26038

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39568

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85964

European-Finnish (FIN)

AF:

0.0000563

AC:

AN:

53282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000424

AC:

AN:

1108744

Other (OTH)

AF:

0.000632

AC:

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.000164

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41452

American (AMR)

AF:

0.000196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.000327

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

0.076

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.021

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

PhyloP100

7.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.91

REVEL

Benign

0.092

Sift

Uncertain

0.017

Sift4G

Benign

0.093

Polyphen

0.74

Vest4

0.21

MVP

0.32

MPC

0.63

ClinPred

0.051

GERP RS

5.3

Varity_R

0.18

gMVP

0.61

Mutation Taster

=54/46

polymorphism

(source)

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

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