chr16-29813073-G-A

Variant names:

• chr16-29813073-G-A
• rs1215479164
• NM_145239.3:c.19G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145239.3(PRRT2):​c.19G>A​(p.Glu7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PRRT2 NM_145239.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• Publications: 1 publications found

Genes affected

PRRT2 (HGNC:30500): (proline rich transmembrane protein 2) This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages. Mutations in this gene are associated with episodic kinesigenic dyskinesia-1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ENSG00000280893 (HGNC:):

MVP-DT (HGNC:56029): (MVP divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11700407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145239.3. 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
	PRRT2	NM_145239.3	MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 2 of 4	NP_660282.2	Q7Z6L0-1
	PRRT2	NM_001256442.2		c.19G>A	p.Glu7Lys	missense	Exon 2 of 3	NP_001243371.1	Q7Z6L0-2
	PRRT2	NM_001438121.1		c.19G>A	p.Glu7Lys	missense	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 2 of 4	ENSP00000351608.7	Q7Z6L0-1
	ENSG00000280893	ENST00000609618.2	TSL:5	n.19G>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2	A0A0G2JLL6
	PRRT2	ENST00000567659.3	TSL:2	c.19G>A	p.Glu7Lys	missense	Exon 2 of 3	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000817 AC: 2 AN: 244780 AF XY: 0.00000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455286 Hom.: 0 Cov.: 32 AF XY: 0.00000553 AC XY: 4 AN XY: 723980

African (AFR) AF: 0.00 AC: 0 AN: 33114

American (AMR) AF: 0.00 AC: 0 AN: 43312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25528

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109112

Other (OTH) AF: 0.00 AC: 0 AN: 60058

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000628 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Episodic kinesigenic dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.077
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.078
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.046	D
Polyphen		0.29	B
Vest4		0.29
MutPred		0.28		Gain of MoRF binding (P = 2e-04)
MVP		0.76
MPC		0.72
ClinPred		0.91	D
GERP RS		2.0
Varity_R		0.13
gMVP		0.27

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: rs1215479164; hg19: chr16-29824394;