rs35732828

Positions:

• chr17-46755851-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006178.4(NSF):​c.*28C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.136 in 1,606,416 control chromosomes in the GnomAD database, including 16,979 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 0.10 (1041 hom., cov: 31)
  • Exomes 𝑓: 0.14 (15938 hom.)
• Consequence: NSF NM_006178.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSF	NM_006178.4	c.*28C>A		3_prime_UTR_variant	21/21	ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2	c.4809+205332C>A		intron_variant			XP_024306541.1
NSF	NR_040116.2	n.2334C>A		non_coding_transcript_exon_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.*28C>A		3_prime_UTR_variant	21/21	1	NM_006178.4	ENSP00000381293	P3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15248 AN: 151322 Hom.: 1041 Cov.: 31

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0877

GnomAD3 exomes AF: 0.107 AC: 26242 AN: 245488 Hom.: 1892 AF XY: 0.109 AC XY: 14468 AN XY: 133196

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.0438

Gnomad ASJ exome AF: 0.0595

Gnomad EAS exome AF: 0.000224

Gnomad SAS exome AF: 0.0775

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.140 AC: 203384 AN: 1454972 Hom.: 15938 Cov.: 31 AF XY: 0.138 AC XY: 99699 AN XY: 723920

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.0610

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0774

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.101 AC: 15246 AN: 151444 Hom.: 1041 Cov.: 31 AF XY: 0.104 AC XY: 7662 AN XY: 73916

Gnomad4 AFR AF: 0.0233

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0868

Alfa AF: 0.115 Hom.: 333

Bravo AF: 0.0843

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.72

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: rs35732828; hg19: chr17-44833217; COSMIC: COSV56574550; COSMIC: COSV56574550;