rs1221627092

Variant names:

• chr14-93779241-C-T
• rs1221627092
• NM_178013.4:c.164G>A

Variant summary

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

The NM_178013.4(PRIMA1):​c.164G>A​(p.Arg55Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000022 in 1,364,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: PRIMA1 NM_178013.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• Publications: 1 publications found

Genes affected

PRIMA1 (HGNC:18319): (proline rich membrane anchor 1) The product of this gene functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes. [provided by RefSeq, Nov 2008]

PRIMA1 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178013.4. 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
	PRIMA1	NM_178013.4	MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 3 of 5	NP_821092.1	Q86XR5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	ENST00000393140.6	TSL:1 MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 3 of 5	ENSP00000376848.1	Q86XR5-1
	PRIMA1	ENST00000393143.5	TSL:1	c.164G>A	p.Arg55Gln	missense	Exon 2 of 4	ENSP00000376851.1	Q86XR5-1
	PRIMA1	ENST00000316227.3	TSL:1	c.164G>A	p.Arg55Gln	missense	Exon 2 of 5	ENSP00000320948.3	Q86XR5-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1364444 Hom.: 0 Cov.: 29 AF XY: 0.00000295 AC XY: 2 AN XY: 677152

African (AFR) AF: 0.00 AC: 0 AN: 27660

American (AMR) AF: 0.00 AC: 0 AN: 27626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23466

East Asian (EAS) AF: 0.00 AC: 0 AN: 34076

South Asian (SAS) AF: 0.0000140 AC: 1 AN: 71232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1070456

Other (OTH) AF: 0.00 AC: 0 AN: 56588

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0054	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Benign	0.075	T
Sift4G	Benign	0.41	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.096		Gain of helix (P = 0.2684)
MVP		0.21
MPC		0.34
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.41
gMVP		0.88
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1221627092; hg19: chr14-94245587;