12-56752285-T-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.14 ( 1584 hom., cov: 31)
Exomes 𝑓: 0.11 ( 9501 hom. )
Consequence
PRIM1
NM_000946.3 missense
NM_000946.3 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 6.99
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 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 id is 1242002.Status of the report is criteria_provided_single_submitter, 1 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRIM1 | NM_000946.3 | c.14A>C | p.Asp5Ala | missense_variant | 1/13 | ENST00000338193.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRIM1 | ENST00000338193.11 | c.14A>C | p.Asp5Ala | missense_variant | 1/13 | 1 | NM_000946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.140 AC: 20847AN: 149232Hom.: 1584 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.124 AC: 24855AN: 200810Hom.: 1677 AF XY: 0.122 AC XY: 13248AN XY: 108188
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GnomAD4 exome AF: 0.112 AC: 160047AN: 1429966Hom.: 9501 Cov.: 30 AF XY: 0.112 AC XY: 79326AN XY: 708726
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GnomAD4 genome ? AF: 0.140 AC: 20869AN: 149350Hom.: 1584 Cov.: 31 AF XY: 0.142 AC XY: 10381AN XY: 73104
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 19, 2019 | This variant is associated with the following publications: (PMID: 30389748) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;.
Polyphen
D;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at