20-1466788-C-G

Position:

• chr20-1466788-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016143.5(NSFL1C):​c.37G>C​(p.Val13Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,410,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NSFL1C NM_016143.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39032006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSFL1C	NM_016143.5	c.37G>C	p.Val13Leu	missense_variant	1/9	ENST00000216879.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSFL1C	ENST00000216879.9	c.37G>C	p.Val13Leu	missense_variant	1/9	1	NM_016143.5	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410032 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 698382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.93	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.48
MutPred		0.38		Loss of phosphorylation at T16 (P = 0.1336);Loss of phosphorylation at T16 (P = 0.1336);Loss of phosphorylation at T16 (P = 0.1336);
MVP		0.53
MPC		1.1
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.55
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1447433;