Variant 17-46694579-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006178.4(NSF):c.1291G>A(p.Val431Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000689 in 1,434,514 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00070 ( 3 hom. )

Consequence

NSF
NM_006178.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

NSF (HGNC:8016): (N-ethylmaleimide sensitive factor, vesicle fusing ATPase) Enables PDZ domain binding activity and ionotropic glutamate receptor binding activity. Involved in intracellular protein transport; positive regulation of protein catabolic process; and positive regulation of receptor recycling. Located in Golgi apparatus; cytosol; and plasma membrane. Implicated in developmental and epileptic encephalopathy. [provided by Alliance of Genome Resources, Apr 2022]

NSF links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024253935).

BP6

Variant 17-46694579-G-A is Benign according to our data. Variant chr17-46694579-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647865.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NSF	NM_006178.4 link	c.1291G>A	p.Val431Met	missense_variant	12/21	ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2 link	c.4809+144060G>A		intron_variant			XP_024306541.1
NSF	NR_040116.2 link	n.1358G>A		non_coding_transcript_exon_variant	11/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8 link	c.1291G>A	p.Val431Met	missense_variant	12/21	1	NM_006178.4	ENSP00000381293.4		P46459-1

Frequencies

GnomAD3 genomes

AF:

0.000573

AC:

AN:

148390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000530

Gnomad ASJ

AF:

0.000581

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000424

Gnomad FIN

AF:

0.0000949

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.000932

Gnomad OTH

AF:

0.000493

GnomAD3 exomes

AF:

0.000699

AC:

AN:

121546

Hom.:

AF XY:

0.000750

AC XY:

AN XY:

62648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.000307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00189

GnomAD4 exome

AF:

0.000702

AC:

903

AN:

1286032

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

472

AN XY:

641606

show subpopulations

Gnomad4 AFR exome

AF:

0.000350

Gnomad4 AMR exome

AF:

0.000972

Gnomad4 ASJ exome

AF:

0.000746

Gnomad4 EAS exome

AF:

0.000106

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000583

Gnomad4 NFE exome

AF:

0.000796

Gnomad4 OTH exome

AF:

0.000650

GnomAD4 genome

AF:

0.000572

AC:

AN:

148482

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

AN XY:

72408

show subpopulations

Gnomad4 AFR

AF:

0.000179

Gnomad4 AMR

AF:

0.000529

Gnomad4 ASJ

AF:

0.000581

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000424

Gnomad4 FIN

AF:

0.0000949

Gnomad4 NFE

AF:

0.000932

Gnomad4 OTH

AF:

0.000488

Alfa

AF:

0.000755

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000623

AC:

ExAC

AF:

0.000464

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

NSF: PP2, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.70

M_CAP

Benign

0.057

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.67

N;.

REVEL

Benign

0.18

Sift

Uncertain

0.027

D;.

Sift4G

Uncertain

0.024

D;D

Polyphen

0.010

B;.

Vest4

0.17

MVP

0.53

MPC

1.9

ClinPred

0.022

GERP RS

0.73

Varity_R

0.049

gMVP

0.56

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over