rs368397994

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_178013.4(PRIMA1):c.228A>T(p.Pro76Pro) 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. 3/3 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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

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 rank	MANE	Protein
PRIMA1	NM_178013.4 link	c.228A>T	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5	ENST00000393140.6	NP_821092.1
PRIMA1	XM_011536456.3 link	c.228A>T	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5		XP_011534758.1
PRIMA1	XM_047430966.1 link	c.228A>T	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5		XP_047286922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PRIMA1	ENST00000393140.6 link	c.228A>T	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5	1	NM_178013.4	ENSP00000376848.1
PRIMA1	ENST00000393143.5 link	c.228A>T	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 2 of 4	1		ENSP00000376851.1
PRIMA1	ENST00000316227.3 link	c.228A>T	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 2 of 5	1		ENSP00000320948.3
PRIMA1	ENST00000477603.5 link	n.228A>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 6	1		ENSP00000434370.1

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

GnomAD2 exomes

AF:

0.0000391

AC:

AN:

127928

AF XY:

0.0000417

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 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

African (AFR)

AF:

0.000327

AC:

AN:

18356

American (AMR)

AF:

0.00

AC:

AN:

11688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9914

East Asian (EAS)

AF:

0.00

AC:

AN:

9092

South Asian (SAS)

AF:

0.00

AC:

AN:

37964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2066

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837884

Other (OTH)

AF:

0.0000298

AC:

AN:

33538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000244

AC:

AN:

45088

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

21140

show subpopulations

African (AFR)

AF:

0.000984

AC:

AN:

11178

American (AMR)

AF:

0.00

AC:

AN:

3274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1160

East Asian (EAS)

AF:

0.00

AC:

AN:

1294

South Asian (SAS)

AF:

0.00

AC:

AN:

1422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

23704

Other (OTH)

AF:

0.00

AC:

AN:

616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial sleep-related hypermotor epilepsy

Uncertain:1

Jun 03, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.84

PhyloP100

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over