Variant 14-93779306-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178013.4(PRIMA1):c.99G>A(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,544,294 control chromosomes in the GnomAD database, including 168,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14766 hom., cov: 29)

Exomes 𝑓: 0.46 ( 153542 hom. )

Consequence

PRIMA1
NM_178013.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.05

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 14-93779306-C-T is Benign according to our data. Variant chr14-93779306-C-T is described in ClinVar as [Benign]. Clinvar id is 586378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRIMA1	NM_178013.4 linkuse as main transcript	c.99G>A	p.Thr33Thr	synonymous_variant	3/5	ENST00000393140.6	NP_821092.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_011536456.3 linkuse as main transcript	c.99G>A	p.Thr33Thr	synonymous_variant	3/5		XP_011534758.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_047430966.1 linkuse as main transcript	c.99G>A	p.Thr33Thr	synonymous_variant	3/5		XP_047286922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRIMA1	ENST00000393140.6 linkuse as main transcript	c.99G>A	p.Thr33Thr	synonymous_variant	3/5	1	NM_178013.4	ENSP00000376848.1	Q86XR5-1
PRIMA1	ENST00000393143.5 linkuse as main transcript	c.99G>A	p.Thr33Thr	synonymous_variant	2/4	1		ENSP00000376851.1	Q86XR5-1
PRIMA1	ENST00000316227.3 linkuse as main transcript	c.99G>A	p.Thr33Thr	synonymous_variant	2/5	1		ENSP00000320948.3	Q86XR5-2
PRIMA1	ENST00000477603.5 linkuse as main transcript	n.99G>A		non_coding_transcript_exon_variant	3/6	1		ENSP00000434370.1	Q86XR5-2

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66106

AN:

151184

Hom.:

14767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.392

AC:

74717

AN:

190516

Hom.:

15563

AF XY:

0.399

AC XY:

42058

AN XY:

105482

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.482

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.463

AC:

645605

AN:

1392992

Hom.:

153542

Cov.:

AF XY:

0.461

AC XY:

318572

AN XY:

691422

show subpopulations

Gnomad4 AFR exome

AF:

0.391

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.253

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.437

AC:

66124

AN:

151302

Hom.:

14766

Cov.:

AF XY:

0.433

AC XY:

32037

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.422

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.424

Hom.:

4728

Bravo

AF:

0.431

Asia WGS

AF:

0.310

AC:

1075

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Sleep-related hypermotor epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

PRIMA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.5

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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