Genetic Variant NM_015980.5: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSG2	NM_015980.5 link	c.*369A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000303177.8	NP_057064.1	Q9Y328

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NSG2	ENST00000303177.8 link	c.*369A>G	3_prime_UTR_variant	Exon 5 of 5	1	NM_015980.5	ENSP00000307722.3	Q9Y328
NSG2	ENST00000521146.1 link	n.786A>G	non_coding_transcript_exon_variant	Exon 3 of 3	2
NSG2	ENST00000521959.5 link	n.830A>G	non_coding_transcript_exon_variant	Exon 4 of 4	2
NSG2	ENST00000521585.5 link	c.213+43559A>G	intron_variant	Intron 3 of 4	4		ENSP00000429863.1	E5RH73

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over