NM_000946.3:c.629C>A

Variant names:

• chr12-56744074-G-T
• NM_000946.3:c.629C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000946.3(PRIM1):​c.629C>A​(p.Pro210His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PRIM1 NM_000946.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIM1	NM_000946.3	c.629C>A	p.Pro210His	missense_variant	Exon 6 of 13	ENST00000338193.11	NP_000937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIM1	ENST00000338193.11	c.629C>A	p.Pro210His	missense_variant	Exon 6 of 13	1	NM_000946.3	ENSP00000350491.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420254 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 702910

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: 9.19e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Uncertain	0.49
Sift	Benign	0.66	T;T
Sift4G	Benign	0.33	T;.
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.73		Gain of catalytic residue at E206 (P = 0.0098);.;
MVP		0.85
MPC		1.1
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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.

Other links and lift over

hg19: chr12-57137858;