rs368397994

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_178013.4(PRIMA1):c.228A>T(p.Pro76=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,029,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

PRIMA1
NM_178013.4 splice_region, synonymous

Scores

Splicing: ADA: 0.1875

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=1.11 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRIMA1	NM_178013.4 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant	3/5	ENST00000393140.6
PRIMA1	XM_011536456.3 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant	3/5
PRIMA1	XM_047430966.1 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMA1	ENST00000393140.6 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant	3/5	1	NM_178013.4	P1	Q86XR5-1
PRIMA1	ENST00000393143.5 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant	2/4	1		P1	Q86XR5-1
PRIMA1	ENST00000316227.3 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant	2/5	1			Q86XR5-2
PRIMA1	ENST00000477603.5 linkuse as main transcript	c.228A>T	p.Pro76=	splice_region_variant, synonymous_variant, NMD_transcript_variant	3/6	1			Q86XR5-2

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

45088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000391

AC:

AN:

127928

Hom.:

AF XY:

0.0000417

AC XY:

AN XY:

72024

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000711

AC:

AN:

984182

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

479096

show subpopulations

Gnomad4 AFR exome

AF:

0.000327

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:

0.00

Gnomad4 OTH exome

AF:

0.0000298

GnomAD4 genome

AF:

0.000244

AC:

AN:

45088

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

21140

show subpopulations

Gnomad4 AFR

AF:

0.000984

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Sleep-related hypermotor epilepsy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jun 03, 2022

This sequence change affects codon 76 of the PRIMA1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PRIMA1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368397994, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with PRIMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 581545). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.19

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over