12-56738452-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

primordial dwarfism-immunodeficiency-lipodystrophy syndrome
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

PRIM1 links:

ENSG00000285625 (HGNC:):

ENSG00000285625 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2672507.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000946.3. 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
	PRIM1	NM_000946.3	MANE Select	c.1126G>A	p.Val376Ile	missense	Exon 11 of 13	NP_000937.1	P49642

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRIM1	ENST00000338193.11	TSL:1 MANE Select	c.1126G>A	p.Val376Ile	missense	Exon 11 of 13	ENSP00000350491.5	P49642
ENSG00000285625	ENST00000647707.1		c.244G>A	p.Val82Ile	missense	Exon 3 of 7	ENSP00000497880.1	A0A3B3ITS8
PRIM1	ENST00000672280.1		c.1243G>A	p.Val415Ile	missense	Exon 12 of 14	ENSP00000500157.1	A0A5F9ZHB6

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

GnomAD2 exomes

AF:

0.00478

AC:

974

AN:

203836

AF XY:

0.00466

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 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

African (AFR)

AF:

0.00191

AC:

AN:

32958

American (AMR)

AF:

0.00627

AC:

251

AN:

40060

Ashkenazi Jewish (ASJ)

AF:

0.00568

AC:

145

AN:

25510

East Asian (EAS)

AF:

0.0000515

AC:

AN:

38864

South Asian (SAS)

AF:

0.000913

AC:

AN:

82180

European-Finnish (FIN)

AF:

0.000702

AC:

AN:

51298

Middle Eastern (MID)

AF:

0.00942

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00960

AC:

10512

AN:

1094796

Other (OTH)

AF:

0.00833

AC:

494

AN:

59282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

637

1275

1912

2550

3187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.00584

AC:

890

AN:

152328

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00272

AC:

113

AN:

41586

American (AMR)

AF:

0.00896

AC:

137

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00880

AC:

599

AN:

68030

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

137

183

229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00788

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.3

(source)

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

PhyloP100

-0.086

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

Mutation Taster

=99/1

polymorphism

(source)

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

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