Variant 12-56738452-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000946.3(PRIM1):c.1126G>A(p.Val376Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 1,583,006 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 58 hom. )

Consequence

PRIM1
NM_000946.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0860

Variant links:

Genes affected

PRIM1 (HGNC:9369): (DNA primase subunit 1) The replication of DNA in eukaryotic cells is carried out by a complex chromosomal replication apparatus, in which DNA polymerase alpha and primase are two key enzymatic components. Primase, which is a heterodimer of a small subunit and a large subunit, synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. The protein encoded by this gene is the small, 49 kDa primase subunit. [provided by RefSeq, Jul 2008]

PRIM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035502613).

BP6

Variant 12-56738452-C-T is Benign according to our data. Variant chr12-56738452-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2672507.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIM1	NM_000946.3 linkuse as main transcript	c.1126G>A	p.Val376Ile	missense_variant	11/13	ENST00000338193.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIM1	ENST00000338193.11 linkuse as main transcript	c.1126G>A	p.Val376Ile	missense_variant	11/13	1	NM_000946.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00585

AC:

890

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00880

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00478

AC:

974

AN:

203836

Hom.:

AF XY:

0.00466

AC XY:

509

AN XY:

109238

show subpopulations

Gnomad AFR exome

AF:

0.00255

Gnomad AMR exome

AF:

0.00529

Gnomad ASJ exome

AF:

0.00689

Gnomad EAS exome

AF:

0.0000650

Gnomad SAS exome

AF:

0.000962

Gnomad FIN exome

AF:

0.000524

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00704

GnomAD4 exome

AF:

0.00813

AC:

11632

AN:

1430678

Hom.:

Cov.:

AF XY:

0.00786

AC XY:

5572

AN XY:

708684

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00627

Gnomad4 ASJ exome

AF:

0.00568

Gnomad4 EAS exome

AF:

0.0000515

Gnomad4 SAS exome

AF:

0.000913

Gnomad4 FIN exome

AF:

0.000702

Gnomad4 NFE exome

AF:

0.00960

Gnomad4 OTH exome

AF:

0.00833

GnomAD4 genome

AF:

0.00584

AC:

890

AN:

152328

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00880

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00776

Hom.:

Bravo

AF:

0.00635

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00134

AC:

ESP6500EA

AF:

0.00843

AC:

ExAC

AF:

0.00301

AC:

362

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

PRIM1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.3

DANN

Benign

0.88

DEOGEN2

Benign

0.00053

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.23

REVEL

Benign

0.032

Sift

Benign

0.20

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.049

MVP

0.18

MPC

0.31

ClinPred

0.0081

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over