rs199533

chr17-46751565-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006178.4(NSF):c.2106G>A(p.Lys702=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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]

LRRC37A2 (HGNC:):

ACMG classification

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	UniProt
NSF	NM_006178.4	c.2106G>A	p.Lys702=	synonymous_variant	19/21	ENST00000398238.8
LRRC37A2	XM_024450773.2	c.4809+201046G>A		intron_variant
NSF	NR_040116.2	n.2173G>A		non_coding_transcript_exon_variant	18/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSF	ENST00000398238.8	c.2106G>A	p.Lys702=	synonymous_variant	19/21	1	NM_006178.4	P3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20347 AN: 152102 Hom.: 1861 Cov.: 32

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

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.: 31 AF XY: 0.180 AC XY: 130793 AN XY: 726742

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.: 32 AF XY: 0.125 AC XY: 9285 AN XY: 74418

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: 91 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

Other links and lift over

dbSNP: rs199533; hg19: chr17-44828931;