dbSNP rs145840548: PRIMA1:p.Ser74Ser (chr14-93779183-G-A) – 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.222C>T(p.Ser74Ser) 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

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: Benign. The variant received -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 VariationId is 476372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PRIMA1	NM_178013.4 link	c.222C>T	p.Ser74Ser	synonymous_variant	Exon 3 of 5	ENST00000393140.6	NP_821092.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_011536456.3 link	c.222C>T	p.Ser74Ser	synonymous_variant	Exon 3 of 5		XP_011534758.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_047430966.1 link	c.222C>T	p.Ser74Ser	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.222C>T	p.Ser74Ser	synonymous_variant	Exon 3 of 5	1	NM_178013.4	ENSP00000376848.1	Q86XR5-1
PRIMA1	ENST00000393143.5 link	c.222C>T	p.Ser74Ser	synonymous_variant	Exon 2 of 4	1		ENSP00000376851.1	Q86XR5-1
PRIMA1	ENST00000316227.3 link	c.222C>T	p.Ser74Ser	synonymous_variant	Exon 2 of 5	1		ENSP00000320948.3	Q86XR5-2
PRIMA1	ENST00000477603.5 link	n.222C>T		non_coding_transcript_exon_variant	Exon 3 of 6	1		ENSP00000434370.1	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

GnomAD2 exomes

AF:

0.00397

AC:

507

AN:

127610

AF XY:

0.00426

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 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

African (AFR)

AF:

0.000815

AC:

AN:

25752

American (AMR)

AF:

0.00208

AC:

AN:

19690

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

21094

East Asian (EAS)

AF:

0.0000945

AC:

AN:

31750

South Asian (SAS)

AF:

0.0000949

AC:

AN:

63210

European-Finnish (FIN)

AF:

0.00534

AC:

265

AN:

49624

Middle Eastern (MID)

AF:

0.00135

AC:

AN:

3712

European-Non Finnish (NFE)

AF:

0.00561

AC:

5858

AN:

1044298

Other (OTH)

AF:

0.00449

AC:

244

AN:

54292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

248

496

744

992

1240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<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:

0.00370

AC:

538

AN:

145600

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

271

AN XY:

70808

show subpopulations

African (AFR)

AF:

0.000816

AC:

AN:

39218

American (AMR)

AF:

0.00413

AC:

AN:

14520

Ashkenazi Jewish (ASJ)

AF:

0.00177

AC:

AN:

3388

East Asian (EAS)

AF:

0.000208

AC:

AN:

4802

South Asian (SAS)

AF:

0.00

AC:

AN:

4406

European-Finnish (FIN)

AF:

0.00531

AC:

AN:

9790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00570

AC:

378

AN:

66290

Other (OTH)

AF:

0.00445

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00440

Hom.:

Bravo

AF:

0.00353

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial sleep-related hypermotor epilepsy

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.0

(source)

DANN

Benign

0.82

PhyloP100

-4.6

Mutation Taster

=100/0

polymorphism

(source)

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

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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