Genetic Variant NM_178013.4:c.99G>C (chr14-93779306-C-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_178013.4(PRIMA1):c.99G>C(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,550,266 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T33T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

PRIMA1
NM_178013.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.05

Publications

11 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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 14-93779306-C-G is Benign according to our data. Variant chr14-93779306-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 586379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

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

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	NM_178013.4	MANE Select	c.99G>C	p.Thr33Thr	synonymous	Exon 3 of 5	NP_821092.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRIMA1	ENST00000393140.6	TSL:1 MANE Select	c.99G>C	p.Thr33Thr	synonymous	Exon 3 of 5	ENSP00000376848.1
PRIMA1	ENST00000393143.5	TSL:1	c.99G>C	p.Thr33Thr	synonymous	Exon 2 of 4	ENSP00000376851.1
PRIMA1	ENST00000316227.3	TSL:1	c.99G>C	p.Thr33Thr	synonymous	Exon 2 of 5	ENSP00000320948.3

Frequencies

GnomAD3 genomes

AF:

0.000482

AC:

AN:

151320

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00356

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:

0.000206

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000341

AC:

AN:

190516

AF XY:

0.000351

show subpopulations

Gnomad AFR exome

AF:

0.0000885

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.000474

GnomAD4 exome

AF:

0.000272

AC:

380

AN:

1398828

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

193

AN XY:

694296

show subpopulations

African (AFR)

AF:

0.0000688

AC:

AN:

29084

American (AMR)

AF:

0.00245

AC:

AN:

33876

Ashkenazi Jewish (ASJ)

AF:

0.0000409

AC:

AN:

24440

East Asian (EAS)

AF:

0.00

AC:

AN:

34868

South Asian (SAS)

AF:

0.00

AC:

AN:

76144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.000255

AC:

277

AN:

1086118

Other (OTH)

AF:

0.000294

AC:

AN:

57798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000482

AC:

AN:

151438

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

AN XY:

73986

show subpopulations

African (AFR)

AF:

0.0000971

AC:

AN:

41196

American (AMR)

AF:

0.00355

AC:

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67864

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.00000869

Hom.:

11502

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.57

(source)

DANN

Benign

0.72

PhyloP100

-1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over