chr20-1453037-C-T

Variant names:

• chr20-1453037-C-T
• rs202113163
• NM_016143.5:c.641G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016143.5(NSFL1C):​c.641G>A​(p.Arg214His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,598,988 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: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: NSFL1C NM_016143.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034807354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016143.5. 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
	NSFL1C	NM_016143.5	MANE Select	c.641G>A	p.Arg214His	missense	Exon 6 of 9	NP_057227.2
	NSFL1C	NM_001206736.2		c.647G>A	p.Arg216His	missense	Exon 7 of 10	NP_001193665.1	Q9UNZ2-5
	NSFL1C	NM_018839.5		c.548G>A	p.Arg183His	missense	Exon 5 of 8	NP_061327.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSFL1C	ENST00000216879.9	TSL:1 MANE Select	c.641G>A	p.Arg214His	missense	Exon 6 of 9	ENSP00000216879.4	Q9UNZ2-1
	NSFL1C	ENST00000926113.1		c.641G>A	p.Arg214His	missense	Exon 6 of 9	ENSP00000596172.1
	NSFL1C	ENST00000855884.1		c.677G>A	p.Arg226His	missense	Exon 7 of 10	ENSP00000525943.1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000490 AC: 123 AN: 251238 AF XY: 0.000449

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00725

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000267 AC: 386 AN: 1446682 Hom.: 0 Cov.: 28 AF XY: 0.000262 AC XY: 189 AN XY: 720930

African (AFR) AF: 0.0000301 AC: 1 AN: 33170

American (AMR) AF: 0.000201 AC: 9 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00595 AC: 155 AN: 26060

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39638

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85968

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.000140 AC: 154 AN: 1098156

Other (OTH) AF: 0.000601 AC: 36 AN: 59898

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74468

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000454 Hom.: 1

Bravo AF: 0.000283

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000436 AC: 53

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.72
MVP		0.77
MPC		1.5
ClinPred		0.13	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.61
Mutation Taster		=43/57	disease causing

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: rs202113163; hg19: chr20-1433682; COSMIC: COSV53792974; COSMIC: COSV53792974;