6-32152121-T-C

Variant names:

• chr6-32152121-T-C
• rs3131283
• ENST00000375150.6:c.-99A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363780.2(PRRT1):​c.-19A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 692,164 control chromosomes in the GnomAD database, including 284,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (63758 hom., cov: 28)
  • Exomes 𝑓: 0.90 (221098 hom.)
• Consequence: PRRT1 NM_001363780.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 42 publications found

Genes affected

PRRT1 (HGNC:13943): (proline rich transmembrane protein 1) Enables identical protein binding activity. Predicted to be involved in several processes, including long-term synaptic depression; protein localization to cell surface; and regulation of AMPA receptor activity. Predicted to act upstream of or within several processes, including learning or memory; long-term synaptic potentiation; and synapse organization. Predicted to be located in postsynaptic density membrane and synaptic vesicle membrane. Predicted to be active in glutamatergic synapse and membrane. Predicted to be integral component of postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285085 (HGNC:):

PPT2 (HGNC:9326): (palmitoyl-protein thioesterase 2) This gene encodes a member of the palmitoyl-protein thioesterase family. The encoded glycosylated lysosomal protein has palmitoyl-CoA hydrolase activity in vitro, but does not hydrolyze palmitate from cysteine residues in proteins. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream EGFL8 (EGF-like-domain, multiple 8) gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363780.2. 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
	PRRT1	NM_001363780.2		c.-19A>G		5_prime_UTR	Exon 2 of 6	NP_001350709.1	Q99946-2
	PRRT1	NM_030651.4	MANE Select	c.-294A>G		upstream_gene	N/A	NP_085154.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRT1	ENST00000375150.6	TSL:1	c.-99A>G		5_prime_UTR	Exon 2 of 6	ENSP00000364292.3	A0A8Z5AAT7
	ENSG00000285085	ENST00000428778.5	TSL:3	c.-99A>G		5_prime_UTR	Exon 3 of 5	ENSP00000396077.2	A2ABC7
	PPT2	ENST00000897785.1		c.-9+1532T>C		intron	N/A	ENSP00000567844.1

Frequencies

GnomAD3 genomes AF: 0.915 AC: 138815 AN: 151768 Hom.: 63695 Cov.: 28

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.936

GnomAD2 exomes AF: 0.920 AC: 137583 AN: 149528 AF XY: 0.922

Gnomad AFR exome AF: 0.981

Gnomad AMR exome AF: 0.950

Gnomad ASJ exome AF: 0.974

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.914

GnomAD4 exome AF: 0.903 AC: 487845 AN: 540278 Hom.: 221098 Cov.: 0 AF XY: 0.907 AC XY: 265167 AN XY: 292286

African (AFR) AF: 0.975 AC: 14995 AN: 15382

American (AMR) AF: 0.950 AC: 32211 AN: 33922

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 18919 AN: 19472

East Asian (EAS) AF: 0.999 AC: 29294 AN: 29324

South Asian (SAS) AF: 0.975 AC: 60231 AN: 61754

European-Finnish (FIN) AF: 0.870 AC: 38744 AN: 44556

Middle Eastern (MID) AF: 0.950 AC: 3772 AN: 3970

European-Non Finnish (NFE) AF: 0.870 AC: 263177 AN: 302582

Other (OTH) AF: 0.904 AC: 26502 AN: 29316

GnomAD4 genome AF: 0.915 AC: 138936 AN: 151886 Hom.: 63758 Cov.: 28 AF XY: 0.917 AC XY: 68023 AN XY: 74210

African (AFR) AF: 0.973 AC: 40333 AN: 41442

American (AMR) AF: 0.937 AC: 14285 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3369 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5128 AN: 5152

South Asian (SAS) AF: 0.973 AC: 4654 AN: 4782

European-Finnish (FIN) AF: 0.884 AC: 9327 AN: 10546

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58737 AN: 67938

Other (OTH) AF: 0.937 AC: 1974 AN: 2106

Alfa AF: 0.889 Hom.: 238009

Bravo AF: 0.922

Asia WGS AF: 0.982 AC: 3416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		-0.89
PromoterAI		-0.013	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3131283; hg19: chr6-32119898;