rs35732828

Variant names:

• chr17-46755851-C-A
• rs35732828
• NM_006178.4:c.*28C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006178.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	NM_006178.4	MANE Select	c.*28C>A		3_prime_UTR	Exon 21 of 21	NP_006169.2	P46459-1
	NSF	NR_040116.2		n.2334C>A		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	ENST00000398238.8	TSL:1 MANE Select	c.*28C>A		3_prime_UTR	Exon 21 of 21	ENSP00000381293.4	P46459-1
	NSF	ENST00000706373.1		c.2217C>A	p.Asp739Glu	missense	Exon 21 of 21	ENSP00000516356.1	A0A994J5X2
	NSF	ENST00000465370.2	TSL:5	c.*52C>A		3_prime_UTR	Exon 22 of 22	ENSP00000467779.2	K7EQD6

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

GnomAD2 exomes AF: 0.107 AC: 26242 AN: 245488 AF XY: 0.109

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 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

African (AFR) AF: 0.0186 AC: 621 AN: 33374

American (AMR) AF: 0.0462 AC: 2051 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.0610 AC: 1589 AN: 26052

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39674

South Asian (SAS) AF: 0.0774 AC: 6603 AN: 85340

European-Finnish (FIN) AF: 0.228 AC: 11911 AN: 52300

Middle Eastern (MID) AF: 0.0389 AC: 224 AN: 5756

European-Non Finnish (NFE) AF: 0.156 AC: 173161 AN: 1107896

Other (OTH) AF: 0.120 AC: 7215 AN: 60154

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

African (AFR) AF: 0.0233 AC: 962 AN: 41276

American (AMR) AF: 0.0723 AC: 1098 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5148

South Asian (SAS) AF: 0.0635 AC: 304 AN: 4786

European-Finnish (FIN) AF: 0.235 AC: 2452 AN: 10426

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9792 AN: 67868

Other (OTH) AF: 0.0868 AC: 181 AN: 2086

Alfa AF: 0.119 Hom.: 997

Bravo AF: 0.0843

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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