Genetic Variant NM_178013.4:c.228A>T (chr14-93779177-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_178013.4(PRIMA1):c.228A>T(p.Pro76Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,029,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

PRIMA1
NM_178013.4 splice_region, synonymous

Scores

Splicing: ADA: 0.1875

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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 Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

PRIMA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=1.11 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	NM_178013.4	MANE Select	c.228A>T	p.Pro76Pro	splice_region synonymous	Exon 3 of 5	NP_821092.1	Q86XR5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRIMA1	ENST00000393140.6	TSL:1 MANE Select	c.228A>T	p.Pro76Pro	splice_region synonymous	Exon 3 of 5	ENSP00000376848.1	Q86XR5-1
PRIMA1	ENST00000393143.5	TSL:1	c.228A>T	p.Pro76Pro	splice_region synonymous	Exon 2 of 4	ENSP00000376851.1	Q86XR5-1
PRIMA1	ENST00000316227.3	TSL:1	c.228A>T	p.Pro76Pro	splice_region synonymous	Exon 2 of 5	ENSP00000320948.3	Q86XR5-2

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

45088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000391

AC:

AN:

127928

AF XY:

0.0000417

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000711

AC:

AN:

984182

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

479096

show subpopulations

African (AFR)

AF:

0.000327

AC:

AN:

18356

American (AMR)

AF:

0.00

AC:

AN:

11688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9914

East Asian (EAS)

AF:

0.00

AC:

AN:

9092

South Asian (SAS)

AF:

0.00

AC:

AN:

37964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2066

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837884

Other (OTH)

AF:

0.0000298

AC:

AN:

33538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000244

AC:

AN:

45088

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

21140

show subpopulations

African (AFR)

AF:

0.000984

AC:

AN:

11178

American (AMR)

AF:

0.00

AC:

AN:

3274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1160

East Asian (EAS)

AF:

0.00

AC:

AN:

1294

South Asian (SAS)

AF:

0.00

AC:

AN:

1422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

23704

Other (OTH)

AF:

0.00

AC:

AN:

616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.19

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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