16-29813694-G-T

Position:

• chr16-29813694-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_145239.3(PRRT2):​c.640G>T​(p.Ala214Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A214P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRRT2 NM_145239.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-29813694-G-CC is described in ClinVar as [Pathogenic]. Clinvar id is 2504178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.23533902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRT2	NM_145239.3	c.640G>T	p.Ala214Ser	missense_variant	2/4	ENST00000358758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRT2	ENST00000358758.12	c.640G>T	p.Ala214Ser	missense_variant	2/4	1	NM_145239.3	P1
MVP-DT	ENST00000569039.5	n.246-3521C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0050	T;.;.;.;.;T;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	.;.;T;T;T;.;T;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.90	L;L;L;.;L;L;.;L;L
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.030	N;.;N;.;N;.;.;.;.
REVEL	Benign	0.12
Sift	Benign	0.045	D;.;D;.;T;.;.;.;.
Sift4G	Benign	0.14	T;.;T;.;T;.;.;T;.
Polyphen		1.0	D;D;D;.;D;D;.;D;D
Vest4		0.19
MutPred		0.12		Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);Gain of phosphorylation at A214 (P = 0.0096);
MVP		0.84
MPC		0.83
ClinPred		0.80	D
GERP RS		3.9
Varity_R		0.078
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs745594874; hg19: chr16-29825015;