NM_145239.3:c.-65-9_-65-7delCTC

Variant names:

• chr16-29812974-TCTC-T
• rs1555502536
• NM_145239.3:c.-65-9_-65-7delCTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_145239.3(PRRT2):​c.-65-9_-65-7delCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,311,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PRRT2 NM_145239.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.887
• Publications: 0 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
• BP6: Variant 16-29812974-TCTC-T is Benign according to our data. Variant chr16-29812974-TCTC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 510853.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-65-9_-65-7delCTC		splice_region intron	N/A	NP_660282.2	Q7Z6L0-1
	PRRT2	NM_001256442.2		c.-65-9_-65-7delCTC		splice_region intron	N/A	NP_001243371.1	Q7Z6L0-2
	PRRT2	NM_001438121.1		c.-65-9_-65-7delCTC		splice_region intron	N/A	NP_001425050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT2	ENST00000358758.12	TSL:1 MANE Select	c.-65-15_-65-13delCTC		intron	N/A	ENSP00000351608.7	Q7Z6L0-1
	ENSG00000280893	ENST00000609618.2	TSL:5	n.-65-15_-65-13delCTC		intron	N/A	ENSP00000476774.2	A0A0G2JLL6
	PRRT2	ENST00000567659.3	TSL:2	c.-65-15_-65-13delCTC		intron	N/A	ENSP00000456226.1	Q7Z6L0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1311074 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 647112

African (AFR) AF: 0.00 AC: 0 AN: 29112

American (AMR) AF: 0.00 AC: 0 AN: 30288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19766

East Asian (EAS) AF: 0.00 AC: 0 AN: 38752

South Asian (SAS) AF: 0.00 AC: 0 AN: 69392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4180

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1016020

Other (OTH) AF: 0.00 AC: 0 AN: 54330

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1555502536; hg19: chr16-29824295;