chr6-32150822-T-G

Position:

• chr6-32150822-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030651.4(PRRT1):​c.104A>C​(p.Gln35Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PRRT1 NM_030651.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08251795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRT1	NM_030651.4	c.104A>C	p.Gln35Pro	missense_variant	2/4	ENST00000211413.10	NP_085154.3
PRRT1	NM_001363780.2	c.100-239A>C		intron_variant			NP_001350709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRT1	ENST00000211413.10	c.104A>C	p.Gln35Pro	missense_variant	2/4	1	NM_030651.4	ENSP00000211413.5
ENSG00000285085	ENST00000428778.5	c.20-239A>C		intron_variant		3		ENSP00000396077.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423314 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 704110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2023

The c.104A>C (p.Q35P) alteration is located in exon 2 (coding exon 2) of the PRRT1 gene. This alteration results from a A to C substitution at nucleotide position 104, causing the glutamine (Q) at amino acid position 35 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.25
Sift	Benign	0.18	T
Sift4G	Benign	0.30	T
Polyphen		0.0050	B
Vest4		0.24
MutPred		0.17		Gain of glycosylation at Q35 (P = 0.0027);
MVP		0.12
ClinPred		0.046	T
GERP RS		1.9
Varity_R		0.13
gMVP		0.24

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: rs967812981; hg19: chr6-32118599;