rs758787026

Positions:

• chr16-29813347-A-C
• chr16-29813347-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145239.3(PRRT2):​c.293A>C​(p.Asn98Thr) 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. 16/21 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. N98S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRRT2 NM_145239.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03232014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRT2	NM_145239.3	c.293A>C	p.Asn98Thr	missense_variant	2/4	ENST00000358758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRT2	ENST00000358758.12	c.293A>C	p.Asn98Thr	missense_variant	2/4	1	NM_145239.3	P1
MVP-DT	ENST00000569039.5	n.246-3174T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251260 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.68
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.66	T;T;.;.;T;T;T;T;T;.;T;.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.032	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
Polyphen		0.0010, 0.0070	.;.;B;B;.;B;.;.;B;B;.;B;B;.
Vest4		0.21, 0.21, 0.19, 0.21
MutPred		0.18		Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);Gain of glycosylation at N98 (P = 0.0012);
MVP		0.33
MPC		0.26
ClinPred		0.039	T
GERP RS		-3.7
Varity_R		0.044
gMVP		0.030

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758787026; hg19: chr16-29824668;