16-29813699-C-T

Variant names:

• chr16-29813699-C-T
• rs183683129
• NM_145239.3:c.645C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_145239.3(PRRT2):​c.645C>T​(p.Pro215Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000766 in 1,580,012 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P215P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000035 (1 hom.)
• Consequence: PRRT2 NM_145239.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.25
• Publications: 4 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 16-29813699-C-T is Benign according to our data. Variant chr16-29813699-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 378432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.

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.645C>T	p.Pro215Pro	synonymous	Exon 2 of 4	NP_660282.2	Q7Z6L0-1
	PRRT2	NM_001256442.2		c.645C>T	p.Pro215Pro	synonymous	Exon 2 of 3	NP_001243371.1	Q7Z6L0-2
	PRRT2	NM_001438121.1		c.645C>T	p.Pro215Pro	synonymous	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.645C>T	p.Pro215Pro	synonymous	Exon 2 of 4	ENSP00000351608.7	Q7Z6L0-1
	ENSG00000280893	ENST00000609618.2	TSL:5	n.645C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2	A0A0G2JLL6
	PRRT2	ENST00000567659.3	TSL:2	c.645C>T	p.Pro215Pro	synonymous	Exon 2 of 3	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes AF: 0.000448 AC: 68 AN: 151888 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000740 AC: 16 AN: 216190 AF XY: 0.0000595

Gnomad AFR exome AF: 0.00109

Gnomad AMR exome AF: 0.0000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000350 AC: 50 AN: 1428004 Hom.: 1 Cov.: 36 AF XY: 0.0000282 AC XY: 20 AN XY: 708286

African (AFR) AF: 0.00112 AC: 36 AN: 32220

American (AMR) AF: 0.000172 AC: 7 AN: 40724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23946

East Asian (EAS) AF: 0.00 AC: 0 AN: 39148

South Asian (SAS) AF: 0.00 AC: 0 AN: 81824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1093958

Other (OTH) AF: 0.0000681 AC: 4 AN: 58710

GnomAD4 genome AF: 0.000467 AC: 71 AN: 152008 Hom.: 0 Cov.: 31 AF XY: 0.000525 AC XY: 39 AN XY: 74306

African (AFR) AF: 0.00147 AC: 61 AN: 41488

American (AMR) AF: 0.000589 AC: 9 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000593 Hom.: 0

Bravo AF: 0.000536

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Episodic kinesigenic dyskinesia (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.6
DANN	Benign	0.84
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs183683129; hg19: chr16-29825020;