dbSNP rs761367817: NAPA:p.Asp96Tyr (chr19-47500642-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003827.4(NAPA):c.286G>T(p.Asp96Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D96N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NAPA
NM_003827.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

NAPA (HGNC:7641): (NSF attachment protein alpha) This gene encodes a member of the soluble NSF attachment protein (SNAP) family. SNAP proteins play a critical role in the docking and fusion of vesicles to target membranes as part of the 20S NSF-SNAP-SNARE complex. The encoded protein plays a role in the completion of membrane fusion by mediating the interaction of N-ethylmaleimide-sensitive factor (NSF) with the vesicle-associated and membrane-associated SNAP receptor (SNARE) complex, and stimulating the ATPase activity of NSF. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jun 2011]

NAPA links:

NAPA-AS1 (HGNC:44118): (NAPA antisense RNA 1)

NAPA-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPA	NM_003827.4 link	c.286G>T	p.Asp96Tyr	missense_variant	Exon 3 of 11	ENST00000263354.8	NP_003818.2	P54920A0A024R0R9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPA	ENST00000263354.8 link	c.286G>T	p.Asp96Tyr	missense_variant	Exon 3 of 11	1	NM_003827.4	ENSP00000263354.2		P54920

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244582

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Uncertain

0.29

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.5

D;.;.

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.0030

D;.;D

Polyphen

1.0

D;.;.

Vest4

0.95

MutPred

0.47

Loss of disorder (P = 0.0332);.;.;

MVP

0.75

MPC

1.0

ClinPred

0.99

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over