chr16-29813493-G-C

Variant names:

• chr16-29813493-G-C
• rs79568162
• NM_145239.3:c.439G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145239.3(PRRT2):​c.439G>C​(p.Asp147His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,613,684 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00053 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (7 hom.)
• Consequence: PRRT2 NM_145239.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.715
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002959013).
• BP6: Variant 16-29813493-G-C is Benign according to our data. Variant chr16-29813493-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000532 (81/152206) while in subpopulation EAS AF = 0.013 (67/5172). AF 95% confidence interval is 0.0105. There are 2 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	NM_145239.3	MANE Select	c.439G>C	p.Asp147His	missense	Exon 2 of 4	NP_660282.2
	PRRT2	NM_001256442.2		c.439G>C	p.Asp147His	missense	Exon 2 of 3	NP_001243371.1
	PRRT2	NM_001438121.1		c.439G>C	p.Asp147His	missense	Exon 2 of 3	NP_001425050.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.439G>C	p.Asp147His	missense	Exon 2 of 4	ENSP00000351608.7
	ENSG00000280893	ENST00000609618.2	TSL:5	n.439G>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000476774.2
	PRRT2	ENST00000567659.3	TSL:2	c.439G>C	p.Asp147His	missense	Exon 2 of 3	ENSP00000456226.1

Frequencies

GnomAD3 genomes AF: 0.000533 AC: 81 AN: 152088 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000991 AC: 248 AN: 250156 AF XY: 0.000909

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0127

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000428 AC: 626 AN: 1461478 Hom.: 7 Cov.: 32 AF XY: 0.000393 AC XY: 286 AN XY: 727006

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0116 AC: 462 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111750

Other (OTH) AF: 0.00247 AC: 149 AN: 60368

GnomAD4 genome AF: 0.000532 AC: 81 AN: 152206 Hom.: 2 Cov.: 31 AF XY: 0.000605 AC XY: 45 AN XY: 74416

African (AFR) AF: 0.000169 AC: 7 AN: 41516

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.0130 AC: 67 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67992

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000771

ExAC AF: 0.000898 AC: 109

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Episodic kinesigenic dyskinesia (1)
-	-	1	Episodic kinesigenic dyskinesia 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	Seizures, benign familial infantile, 2;C1865926:Infantile convulsions and choreoathetosis;C4552000:Episodic kinesigenic dyskinesia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.71
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.085
Sift	Uncertain	0.026	D
Sift4G	Benign	0.10	T
Polyphen		0.33	B
Vest4		0.10
MVP		0.71
MPC		0.72
ClinPred		0.012	T
GERP RS		2.0
Varity_R		0.046
gMVP		0.073
Mutation Taster		=99/1	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

dbSNP: rs79568162; hg19: chr16-29824814; COSMIC: COSV54882607; COSMIC: COSV54882607;