Genetic Variant PRM3:p.Glu62Gln (chr16-11273412-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021247.3(PRM3):c.184G>C(p.Glu62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000715 in 1,397,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

PRM3
NM_021247.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

PRM3 (HGNC:13732): (protamine 3) Predicted to enable DNA binding activity. Predicted to be involved in flagellated sperm motility. Predicted to be located in nucleus. Predicted to be part of nucleosome. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRM3 links:

RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

RMI2 links:

LOC105371082 (HGNC:):

LOC105371082 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17987639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRM3	NM_021247.3 link	c.184G>C	p.Glu62Gln	missense_variant	Exon 1 of 1	ENST00000327157.4	NP_067070.2	Q9NNZ6
LOC105371082	XR_933070.4 link	n.178+23634C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRM3	ENST00000327157.4 link	c.184G>C	p.Glu62Gln	missense_variant	Exon 1 of 1	6	NM_021247.3	ENSP00000325638.2	Q9NNZ6
RMI2	ENST00000572173.1 link	c.-515-21804C>G		intron_variant	Intron 1 of 4	1		ENSP00000461206.1	Q96E14-2
RMI2	ENST00000573910.1 link	n.160+23634C>G		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1 link	n.152+23634C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000715

AC:

AN:

1397958

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000741

Gnomad4 OTH exome

AF:

0.0000172

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

Dec 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.184G>C (p.E62Q) alteration is located in exon 1 (coding exon 1) of the PRM3 gene. This alteration results from a G to C substitution at nucleotide position 184, causing the glutamic acid (E) at amino acid position 62 to be replaced by a glutamine (Q). 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

Benign

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.50

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.14

Sift

Uncertain

0.011

Sift4G

Pathogenic

0.0

Vest4

0.28

MutPred

0.14

Loss of loop (P = 0.0145);

MVP

0.20

ClinPred

0.78

GERP RS

3.9

gMVP

0.028

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