20-1464381-C-G

Variant names:

• chr20-1464381-C-G
• NM_016143.5:c.151G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016143.5(NSFL1C):​c.151G>C​(p.Val51Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NSFL1C NM_016143.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14250031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSFL1C	NM_016143.5	c.151G>C	p.Val51Leu	missense_variant	Exon 2 of 9	ENST00000216879.9	NP_057227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSFL1C	ENST00000216879.9	c.151G>C	p.Val51Leu	missense_variant	Exon 2 of 9	1	NM_016143.5	ENSP00000216879.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151G>C (p.V51L) alteration is located in exon 2 (coding exon 2) of the NSFL1C gene. This alteration results from a G to C substitution at nucleotide position 151, causing the valine (V) at amino acid position 51 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.023	.;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.77	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.18
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0507);Gain of relative solvent accessibility (P = 0.0507);Gain of relative solvent accessibility (P = 0.0507);
MVP		0.57
MPC		0.44
ClinPred		0.51	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.24

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: chr20-1445026;