Genetic Variant NSG2:c.*369A>G (chr5-174107874-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015980.5(NSG2):c.*369A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 401,606 control chromosomes in the GnomAD database, including 19,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 11674 hom., cov: 32)

Exomes 𝑓: 0.23 ( 7594 hom. )

Consequence

NSG2
NM_015980.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.796

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSG2	NM_015980.5	MANE Select	c.*369A>G		3_prime_UTR	Exon 5 of 5	NP_057064.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NSG2	ENST00000303177.8	TSL:1 MANE Select	c.*369A>G	3_prime_UTR	Exon 5 of 5	ENSP00000307722.3
NSG2	ENST00000521146.1	TSL:2	n.786A>G	non_coding_transcript_exon	Exon 3 of 3
NSG2	ENST00000521959.5	TSL:2	n.830A>G	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51130

AN:

151964

Hom.:

11633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.0945

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.320

GnomAD4 exome

AF:

0.231

AC:

57534

AN:

249524

Hom.:

7594

Cov.:

AF XY:

0.230

AC XY:

32055

AN XY:

139350

show subpopulations

African (AFR)

AF:

0.644

AC:

4345

AN:

6752

American (AMR)

AF:

0.203

AC:

3834

AN:

18916

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

1567

AN:

6588

East Asian (EAS)

AF:

0.0909

AC:

882

AN:

9704

South Asian (SAS)

AF:

0.239

AC:

11215

AN:

46992

European-Finnish (FIN)

AF:

0.188

AC:

1939

AN:

10334

Middle Eastern (MID)

AF:

0.310

AC:

597

AN:

1926

European-Non Finnish (NFE)

AF:

0.222

AC:

30223

AN:

136204

Other (OTH)

AF:

0.242

AC:

2932

AN:

12108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2534

5068

7602

10136

12670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.337

AC:

51229

AN:

152082

Hom.:

11674

Cov.:

AF XY:

0.329

AC XY:

24445

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.648

AC:

26856

AN:

41448

American (AMR)

AF:

0.254

AC:

3874

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

828

AN:

3466

East Asian (EAS)

AF:

0.0947

AC:

490

AN:

5174

South Asian (SAS)

AF:

0.246

AC:

1185

AN:

4820

European-Finnish (FIN)

AF:

0.187

AC:

1983

AN:

10582

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14959

AN:

67994

Other (OTH)

AF:

0.325

AC:

686

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1473

2946

4420

5893

7366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.272

Hom.:

16891

Bravo

AF:

0.359

Asia WGS

AF:

0.240

AC:

833

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.1

(source)

DANN

Benign

0.54

PhyloP100

0.80

Mutation Taster

=99/1

polymorphism (auto)

(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

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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