19-47492073-T-C

Variant names:

• chr19-47492073-T-C
• NM_003827.4:c.608A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003827.4(NAPA):​c.608A>G​(p.Lys203Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAPA NM_003827.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96
• Publications: 0 publications found

Genes affected

NAPA (HGNC:7641): (NSF attachment protein alpha) This gene encodes a member of the soluble NSF attachment protein (SNAP) family. SNAP proteins play a critical role in the docking and fusion of vesicles to target membranes as part of the 20S NSF-SNAP-SNARE complex. The encoded protein plays a role in the completion of membrane fusion by mediating the interaction of N-ethylmaleimide-sensitive factor (NSF) with the vesicle-associated and membrane-associated SNAP receptor (SNARE) complex, and stimulating the ATPase activity of NSF. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jun 2011]

NAPA-AS1 (HGNC:44118): (NAPA antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003827.4. 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
	NAPA	NM_003827.4	MANE Select	c.608A>G	p.Lys203Arg	missense	Exon 8 of 11	NP_003818.2
	NAPA	NR_038456.2		n.731A>G		non_coding_transcript_exon	Exon 8 of 12
	NAPA	NR_038457.2		n.534A>G		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPA	ENST00000263354.8	TSL:1 MANE Select	c.608A>G	p.Lys203Arg	missense	Exon 8 of 11	ENSP00000263354.2	P54920
	NAPA	ENST00000593761.5	TSL:5	c.638A>G	p.Lys213Arg	missense	Exon 8 of 10	ENSP00000472667.1	M0R2M1
	NAPA	ENST00000595227.5	TSL:3	c.491A>G	p.Lys164Arg	missense	Exon 7 of 10	ENSP00000471520.1	M0R0Y2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.21
Sift	Benign	0.14	T
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.90
MutPred		0.75		Gain of catalytic residue at K203 (P = 0.0101)
MVP		0.57
MPC		0.57
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.35
gMVP		0.66
Mutation Taster		=78/22	polymorphism

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

hg19: chr19-47995330;