Variant 12-56752271-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000946.3(PRIM1):c.28C>T(p.Pro10Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRIM1
NM_000946.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.68

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRIM1	NM_000946.3 link	c.28C>T	p.Pro10Ser	missense_variant	1/13	ENST00000338193.11	NP_000937.1	P49642

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRIM1	ENST00000338193.11 link	c.28C>T	p.Pro10Ser	missense_variant	1/13	1	NM_000946.3	ENSP00000350491.5		P49642

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1440076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714288

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.28C>T (p.P10S) alteration is located in exon 1 (coding exon 1) of the PRIM1 gene. This alteration results from a C to T substitution at nucleotide position 28, causing the proline (P) at amino acid position 10 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.18

Sift

Benign

0.14

T;T

Sift4G

Benign

0.28

T;.

Polyphen

1.0

D;.

Vest4

0.45

MutPred

0.41

Gain of catalytic residue at L9 (P = 0.0061);Gain of catalytic residue at L9 (P = 0.0061);

MVP

0.48

MPC

0.67

ClinPred

0.99

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.54

gMVP

0.59

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

No publications associated with this variant yet.

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