Variant rs199533 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006178.4(NSF):c.2106G>A(p.Lys702Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,040 control chromosomes in the GnomAD database, including 29,444 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 0.13 ( 1859 hom., cov: 32)

Exomes 𝑓: 0.18 ( 27585 hom. )

Consequence

NSF
NM_006178.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.551

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=-0.551 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NSF	NM_006178.4 link	c.2106G>A	p.Lys702Lys	synonymous_variant	19/21	ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2 link	c.4809+201046G>A		intron_variant			XP_024306541.1
NSF	NR_040116.2 link	n.2173G>A		non_coding_transcript_exon_variant	18/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8 link	c.2106G>A	p.Lys702Lys	synonymous_variant	19/21	1	NM_006178.4	ENSP00000381293.4		P46459-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20347

AN:

152102

Hom.:

1861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.0718

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.135

AC:

33609

AN:

249156

Hom.:

3006

AF XY:

0.136

AC XY:

18409

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.0338

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.000612

Gnomad SAS exome

AF:

0.0613

Gnomad FIN exome

AF:

0.0717

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.183

AC:

267137

AN:

1460820

Hom.:

27585

Cov.:

AF XY:

0.180

AC XY:

130793

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.0315

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.000832

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.0767

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.134

AC:

20332

AN:

152220

Hom.:

1859

Cov.:

AF XY:

0.125

AC XY:

9285

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0602

Gnomad4 FIN

AF:

0.0718

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.192

Hom.:

7849

Bravo

AF:

0.138

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.3

DANN

Benign

0.86

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