dbSNP rs2274870: NIPSNAP3A:p.Arg100Gln (chr9-104752933-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015469.3(NIPSNAP3A):c.299G>A(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,611,216 control chromosomes in the GnomAD database, including 318,828 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 0.65 ( 33043 hom., cov: 32)

Exomes 𝑓: 0.62 ( 285785 hom. )

Consequence

NIPSNAP3A
NM_015469.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.952

Publications

41 publications found

Variant links:

Genes affected

NIPSNAP3A (HGNC:23619): (nipsnap homolog 3A) NIPSNAP3A belongs to a family of proteins with putative roles in vesicular transport (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

NIPSNAP3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=2.0465527E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3A	NM_015469.3 link	c.299G>A	p.Arg100Gln	missense_variant	Exon 3 of 6	ENST00000374767.5	NP_056284.1	Q9UFN0
NIPSNAP3A	NM_001329570.2 link	c.299G>A	p.Arg100Gln	missense_variant	Exon 3 of 5		NP_001316499.1	Q9UFN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPSNAP3A	ENST00000374767.5 link	c.299G>A	p.Arg100Gln	missense_variant	Exon 3 of 6	1	NM_015469.3	ENSP00000363899.4		Q9UFN0

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99323

AN:

151814

Hom.:

33002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.744

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.681

GnomAD2 exomes

AF:

0.621

AC:

155963

AN:

251176

AF XY:

0.616

show subpopulations

Gnomad AFR exome

AF:

0.744

Gnomad AMR exome

AF:

0.683

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.625

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.624

AC:

910249

AN:

1459284

Hom.:

285785

Cov.:

AF XY:

0.622

AC XY:

451959

AN XY:

726060

show subpopulations

African (AFR)

AF:

0.747

AC:

24955

AN:

33420

American (AMR)

AF:

0.685

AC:

30612

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.744

AC:

19415

AN:

26112

East Asian (EAS)

AF:

0.555

AC:

21996

AN:

39668

South Asian (SAS)

AF:

0.581

AC:

50030

AN:

86146

European-Finnish (FIN)

AF:

0.479

AC:

25569

AN:

53410

Middle Eastern (MID)

AF:

0.723

AC:

4162

AN:

5758

European-Non Finnish (NFE)

AF:

0.626

AC:

694828

AN:

1109738

Other (OTH)

AF:

0.641

AC:

38682

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16138

32276

48414

64552

80690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18598

37196

55794

74392

92990

<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:

0.654

AC:

99418

AN:

151932

Hom.:

33043

Cov.:

AF XY:

0.648

AC XY:

48109

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.745

AC:

30892

AN:

41466

American (AMR)

AF:

0.712

AC:

10863

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.742

AC:

2575

AN:

3472

East Asian (EAS)

AF:

0.544

AC:

2812

AN:

5166

South Asian (SAS)

AF:

0.578

AC:

2780

AN:

4808

European-Finnish (FIN)

AF:

0.465

AC:

4884

AN:

10494

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.625

AC:

42463

AN:

67950

Other (OTH)

AF:

0.674

AC:

1421

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1768

3536

5305

7073

8841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.642

Hom.:

70786

Bravo

AF:

0.675

TwinsUK

AF:

0.626

AC:

2322

ALSPAC

AF:

0.625

AC:

2407

ESP6500AA

AF:

0.753

AC:

3317

ESP6500EA

AF:

0.636

AC:

5471

ExAC

AF:

0.618

AC:

75006

Asia WGS

AF:

0.525

AC:

1828

AN:

3478

EpiCase

AF:

0.644

EpiControl

AF:

0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

PhyloP100

0.95

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.26

Sift

Benign

0.039

Sift4G

Uncertain

0.023

Polyphen

0.95

Vest4

0.068

MPC

0.33

ClinPred

0.024

GERP RS

1.3

Varity_R

0.46

gMVP

0.88

Mutation Taster

=80/20

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