20-1449559-C-T

Variant names:

• chr20-1449559-C-T
• rs6105165
• NM_016143.5:c.785+2934G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016143.5(NSFL1C):​c.785+2934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,100 control chromosomes in the GnomAD database, including 13,093 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 0.40 (13093 hom., cov: 32)
• Consequence: NSFL1C NM_016143.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 12 publications found

Genes affected

NSFL1C (HGNC:15912): (NSFL1 cofactor) N-ethylmaleimide-sensitive factor (NSF) and valosin-containing protein (p97) are two ATPases known to be involved in transport vesicle/target membrane fusion and fusions between membrane compartments. A trimer of the protein encoded by this gene binds a hexamer of cytosolic p97 and is required for p97-mediated regrowth of Golgi cisternae from mitotic Golgi fragments. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 8. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSFL1C	NM_016143.5	c.785+2934G>A		intron_variant	Intron 7 of 8	ENST00000216879.9	NP_057227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSFL1C	ENST00000216879.9	c.785+2934G>A		intron_variant	Intron 7 of 8	1	NM_016143.5	ENSP00000216879.4

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61230 AN: 151982 Hom.: 13082 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 61276 AN: 152100 Hom.: 13093 Cov.: 32 AF XY: 0.406 AC XY: 30211 AN XY: 74352

African (AFR) AF: 0.296 AC: 12280 AN: 41484

American (AMR) AF: 0.482 AC: 7358 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4044 AN: 5180

South Asian (SAS) AF: 0.428 AC: 2065 AN: 4826

European-Finnish (FIN) AF: 0.412 AC: 4361 AN: 10580

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28497 AN: 67966

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.412 Hom.: 1637

Bravo AF: 0.407

Asia WGS AF: 0.579 AC: 2010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		1.8
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: rs6105165; hg19: chr20-1430204;