rs199533

Variant names:

• chr17-46751565-G-A
• rs199533
• NM_006178.4:c.2106G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-46751565-G-A
• chr17-46751565-G-C
• chr17-46751565-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 144 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 -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.

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.2106G>A	p.Lys702Lys	synonymous	Exon 19 of 21	NP_006169.2	P46459-1
	NSF	NR_040116.2		n.2173G>A		non_coding_transcript_exon	Exon 18 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	ENST00000398238.8	TSL:1 MANE Select	c.2106G>A	p.Lys702Lys	synonymous	Exon 19 of 21	ENSP00000381293.4	P46459-1
	NSF	ENST00000465370.2	TSL:5	c.2106G>A	p.Lys702Lys	synonymous	Exon 19 of 22	ENSP00000467779.2	K7EQD6
	NSF	ENST00000706392.1		c.2106G>A	p.Lys702Lys	synonymous	Exon 19 of 22	ENSP00000516369.1	P46459-1

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

GnomAD2 exomes AF: 0.135 AC: 33609 AN: 249156 AF XY: 0.136

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 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

African (AFR) AF: 0.0315 AC: 1055 AN: 33474

American (AMR) AF: 0.118 AC: 5290 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5888 AN: 26124

East Asian (EAS) AF: 0.000832 AC: 33 AN: 39684

South Asian (SAS) AF: 0.0651 AC: 5607 AN: 86192

European-Finnish (FIN) AF: 0.0767 AC: 4099 AN: 53414

Middle Eastern (MID) AF: 0.177 AC: 1019 AN: 5766

European-Non Finnish (NFE) AF: 0.211 AC: 234104 AN: 1111114

Other (OTH) AF: 0.166 AC: 10042 AN: 60366

GnomAD4 genome AF: 0.134 AC: 20332 AN: 152220 Hom.: 1859 Cov.: 32 AF XY: 0.125 AC XY: 9285 AN XY: 74418

African (AFR) AF: 0.0364 AC: 1513 AN: 41546

American (AMR) AF: 0.164 AC: 2500 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0602 AC: 290 AN: 4820

European-Finnish (FIN) AF: 0.0718 AC: 761 AN: 10594

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13881 AN: 67996

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.183 Hom.: 14417

Bravo AF: 0.138

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.3
DANN	Benign	0.86
PhyloP100		-0.55
Mutation Taster		=98/2	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: rs199533; hg19: chr17-44828931; COSMIC: COSV108082174;