Variant rs145840548 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_178013.4(PRIMA1):c.222C>T(p.Ser74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,459,022 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 22)

Exomes 𝑓: 0.0049 ( 20 hom. )

Consequence

PRIMA1
NM_178013.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.63

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 14-93779183-G-A is Benign according to our data. Variant chr14-93779183-G-A is described in ClinVar as [Benign]. Clinvar id is 476372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-93779183-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.64 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRIMA1	NM_178013.4 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant	3/5	ENST00000393140.6
PRIMA1	XM_011536456.3 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant	3/5
PRIMA1	XM_047430966.1 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMA1	ENST00000393140.6 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant	3/5	1	NM_178013.4	P1	Q86XR5-1
PRIMA1	ENST00000393143.5 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant	2/4	1		P1	Q86XR5-1
PRIMA1	ENST00000316227.3 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant	2/5	1			Q86XR5-2
PRIMA1	ENST00000477603.5 linkuse as main transcript	c.222C>T	p.Ser74=	synonymous_variant, NMD_transcript_variant	3/6	1			Q86XR5-2

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

538

AN:

145498

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000818

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00414

Gnomad ASJ

AF:

0.00177

Gnomad EAS

AF:

0.000208

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00531

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00570

Gnomad OTH

AF:

0.00450

GnomAD3 exomes

AF:

0.00397

AC:

507

AN:

127610

Hom.:

AF XY:

0.00426

AC XY:

305

AN XY:

71570

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00147

Gnomad EAS exome

AF:

0.000136

Gnomad SAS exome

AF:

0.000221

Gnomad FIN exome

AF:

0.00528

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00493

AC:

6477

AN:

1313422

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

3036

AN XY:

649444

show subpopulations

Gnomad4 AFR exome

AF:

0.000815

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0000945

Gnomad4 SAS exome

AF:

0.0000949

Gnomad4 FIN exome

AF:

0.00534

Gnomad4 NFE exome

AF:

0.00561

Gnomad4 OTH exome

AF:

0.00449

GnomAD4 genome

AF:

0.00370

AC:

538

AN:

145600

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

271

AN XY:

70808

show subpopulations

Gnomad4 AFR

AF:

0.000816

Gnomad4 AMR

AF:

0.00413

Gnomad4 ASJ

AF:

0.00177

Gnomad4 EAS

AF:

0.000208

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00531

Gnomad4 NFE

AF:

0.00570

Gnomad4 OTH

AF:

0.00445

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.00353

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sleep-related hypermotor epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.0

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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