Variant 17-46713956-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006178.4(NSF):c.1731T>C(p.Ser577Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,606,030 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 35 hom. )

Consequence

NSF
NM_006178.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.240

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:

NSF (HGNC:):

NSF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 17-46713956-T-C is Benign according to our data. Variant chr17-46713956-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 775110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.24 with no splicing effect.

BS2

High AC in GnomAd4 at 668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NSF	NM_006178.4 linkuse as main transcript	c.1731T>C	p.Ser577Ser	synonymous_variant	15/21	ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2 linkuse as main transcript	c.4809+163437T>C		intron_variant			XP_024306541.1
NSF	NR_040116.2 linkuse as main transcript	n.1798T>C		non_coding_transcript_exon_variant	14/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8 linkuse as main transcript	c.1731T>C	p.Ser577Ser	synonymous_variant	15/21	1	NM_006178.4	ENSP00000381293.4		P46459-1

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

670

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00418

AC:

1005

AN:

240186

Hom.:

AF XY:

0.00448

AC XY:

583

AN XY:

130120

show subpopulations

Gnomad AFR exome

AF:

0.000783

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.00802

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00435

Gnomad FIN exome

AF:

0.000652

Gnomad NFE exome

AF:

0.00624

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.00612

AC:

8894

AN:

1453710

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

4426

AN XY:

722662

show subpopulations

Gnomad4 AFR exome

AF:

0.000878

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.00731

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00511

Gnomad4 FIN exome

AF:

0.000787

Gnomad4 NFE exome

AF:

0.00704

Gnomad4 OTH exome

AF:

0.00449

GnomAD4 genome

AF:

0.00439

AC:

668

AN:

152320

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

334

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00605

Hom.:

Bravo

AF:

0.00402

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	NSF: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 27, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.6

DANN

Benign

0.70

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