dbSNP rs4900195: PRIMA1:p.Thr33Thr (chr14-93779306-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_178013.4(PRIMA1):c.99G>T(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRIMA1
NM_178013.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 14-93779306-C-A is Benign according to our data. Variant chr14-93779306-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1130704.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMA1	NM_178013.4 link	c.99G>T	p.Thr33Thr	synonymous_variant	Exon 3 of 5	ENST00000393140.6	NP_821092.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_011536456.3 link	c.99G>T	p.Thr33Thr	synonymous_variant	Exon 3 of 5		XP_011534758.1	Q86XR5-1A0A024R6J9
PRIMA1	XM_047430966.1 link	c.99G>T	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>T	p.Thr33Thr	synonymous_variant	Exon 3 of 5	1	NM_178013.4	ENSP00000376848.1	Q86XR5-1
PRIMA1	ENST00000393143.5 link	c.99G>T	p.Thr33Thr	synonymous_variant	Exon 2 of 4	1		ENSP00000376851.1	Q86XR5-1
PRIMA1	ENST00000316227.3 link	c.99G>T	p.Thr33Thr	synonymous_variant	Exon 2 of 5	1		ENSP00000320948.3	Q86XR5-2
PRIMA1	ENST00000477603.5 link	n.99G>T		non_coding_transcript_exon_variant	Exon 3 of 6	1		ENSP00000434370.1	Q86XR5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.15e-7

AC:

AN:

1398832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29084

American (AMR)

AF:

0.00

AC:

AN:

33876

Ashkenazi Jewish (ASJ)

AF:

0.00

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:

9.21e-7

AC:

AN:

1086122

Other (OTH)

AF:

0.00

AC:

AN:

57798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

11502

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial sleep-related hypermotor epilepsy

Benign:1

Jul 21, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.80

(source)

DANN

Benign

0.81

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over