14-93779306-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. T33T) has been classified as Likely 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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRIMA1	NM_178013.4 link	c.99G>A	p.Thr33Thr	synonymous_variant	Exon 3 of 5	ENST00000393140.6	NP_821092.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_011536456.3 link	c.99G>A	p.Thr33Thr	synonymous_variant	Exon 3 of 5		XP_011534758.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_047430966.1 link	c.99G>A	p.Thr33Thr	synonymous_variant	Exon 3 of 5		XP_047286922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRIMA1	ENST00000393140.6 link	c.99G>A	p.Thr33Thr	synonymous_variant	Exon 3 of 5	1	NM_178013.4	ENSP00000376848.1	Q86XR5-1
PRIMA1	ENST00000393143.5 link	c.99G>A	p.Thr33Thr	synonymous_variant	Exon 2 of 4	1		ENSP00000376851.1	Q86XR5-1
PRIMA1	ENST00000316227.3 link	c.99G>A	p.Thr33Thr	synonymous_variant	Exon 2 of 5	1		ENSP00000320948.3	Q86XR5-2
PRIMA1	ENST00000477603.5 link	n.99G>A		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.392

AC:

74717

AN:

190516

AF XY:

0.399

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 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

African (AFR)

AF:

0.391

AC:

11308

AN:

28896

American (AMR)

AF:

0.282

AC:

9459

AN:

33558

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

9728

AN:

24318

East Asian (EAS)

AF:

0.253

AC:

8806

AN:

34804

South Asian (SAS)

AF:

0.352

AC:

26540

AN:

75442

European-Finnish (FIN)

AF:

0.484

AC:

24499

AN:

50660

Middle Eastern (MID)

AF:

0.403

AC:

2258

AN:

5598

European-Non Finnish (NFE)

AF:

0.487

AC:

527073

AN:

1082138

Other (OTH)

AF:

0.450

AC:

25934

AN:

57578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

15180

30360

45539

60719

75899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.437

AC:

66124

AN:

151302

Hom.:

14766

Cov.:

AF XY:

0.433

AC XY:

32037

AN XY:

73918

show subpopulations

African (AFR)

AF:

0.401

AC:

16478

AN:

41138

American (AMR)

AF:

0.422

AC:

6409

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1344

AN:

3464

East Asian (EAS)

AF:

0.231

AC:

1179

AN:

5114

South Asian (SAS)

AF:

0.355

AC:

1695

AN:

4780

European-Finnish (FIN)

AF:

0.487

AC:

5095

AN:

10470

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.478

AC:

32446

AN:

67844

Other (OTH)

AF:

0.452

AC:

952

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1772

3543

5315

7086

8858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.436

Hom.:

11502

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial sleep-related hypermotor epilepsy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PRIMA1-related disorder

Benign:1

Jul 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.83

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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14-93779306-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over