NM_000946.3:c.14A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000946.3(PRIM1):c.14A>C(p.Asp5Ala) variant causes a missense change. The variant allele was found at a frequency of 0.115 in 1,579,316 control chromosomes in the GnomAD database, including 11,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1584 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9501 hom. )

Consequence

PRIM1
NM_000946.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.99

Publications

118 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 links:

HSD17B6 (HGNC:23316): (hydroxysteroid 17-beta dehydrogenase 6) The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013]

HSD17B6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016110837).

BP6

Variant 12-56752285-T-G is Benign according to our data. Variant chr12-56752285-T-G is described in ClinVar as Benign. ClinVar VariationId is 1242002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIM1	NM_000946.3 link	c.14A>C	p.Asp5Ala	missense_variant	Exon 1 of 13	ENST00000338193.11	NP_000937.1	P49642

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIM1	ENST00000338193.11 link	c.14A>C	p.Asp5Ala	missense_variant	Exon 1 of 13	1	NM_000946.3	ENSP00000350491.5		P49642

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

20847

AN:

149232

Hom.:

1584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.0930

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.141

GnomAD2 exomes

AF:

0.124

AC:

24855

AN:

200810

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.112

AC:

160047

AN:

1429966

Hom.:

9501

Cov.:

AF XY:

0.112

AC XY:

79326

AN XY:

708726

show subpopulations

African (AFR)

AF:

0.205

AC:

6697

AN:

32622

American (AMR)

AF:

0.121

AC:

4878

AN:

40258

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3220

AN:

25568

East Asian (EAS)

AF:

0.212

AC:

8075

AN:

38040

South Asian (SAS)

AF:

0.105

AC:

8601

AN:

81936

European-Finnish (FIN)

AF:

0.133

AC:

6824

AN:

51180

Middle Eastern (MID)

AF:

0.203

AC:

1164

AN:

5730

European-Non Finnish (NFE)

AF:

0.104

AC:

113455

AN:

1095456

Other (OTH)

AF:

0.121

AC:

7133

AN:

59176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6263

12526

18790

25053

31316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4340

8680

13020

17360

21700

<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:

0.140

AC:

20869

AN:

149350

Hom.:

1584

Cov.:

AF XY:

0.142

AC XY:

10381

AN XY:

73104

show subpopulations

African (AFR)

AF:

0.202

AC:

8187

AN:

40584

American (AMR)

AF:

0.121

AC:

1827

AN:

15088

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

417

AN:

3436

East Asian (EAS)

AF:

0.219

AC:

1101

AN:

5020

South Asian (SAS)

AF:

0.0941

AC:

445

AN:

4728

European-Finnish (FIN)

AF:

0.145

AC:

1511

AN:

10400

Middle Eastern (MID)

AF:

0.164

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.104

AC:

6919

AN:

66846

Other (OTH)

AF:

0.141

AC:

293

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

928

1855

2783

3710

4638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.116

Hom.:

5280

Bravo

AF:

0.141

TwinsUK

AF:

0.0987

AC:

366

ALSPAC

AF:

0.107

AC:

413

ESP6500AA

AF:

0.181

AC:

705

ESP6500EA

AF:

0.0947

AC:

784

ExAC

AF:

0.106

AC:

12628

Asia WGS

AF:

0.128

AC:

444

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30389748) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;.

PhyloP100

7.0

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.014

D;.

Polyphen

0.99

D;.

Vest4

0.29

MPC

1.1

ClinPred

0.030

GERP RS

4.7

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.69

gMVP

0.54

Mutation Taster

=262/38

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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