Genetic Variant PRM3:p.Arg100Gln (chr16-11273297-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_021247.3(PRM3):c.299G>A(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 1,541,062 control chromosomes in the GnomAD database, including 631,932 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 56236 hom., cov: 33)

Exomes 𝑓: 0.91 ( 575696 hom. )

Consequence

PRM3
NM_021247.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.431

Publications

15 publications found

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:

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=8.7458506E-7).

BP6

Variant 16-11273297-C-T is Benign according to our data. Variant chr16-11273297-C-T is described in ClinVar as Benign. ClinVar VariationId is 1241438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021247.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM3	NM_021247.3	MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 1 of 1	NP_067070.2	Q9NNZ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRM3	ENST00000327157.4	TSL:6 MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 1 of 1	ENSP00000325638.2	Q9NNZ6
RMI2	ENST00000572173.1	TSL:1	c.-515-21919C>T		intron	N/A	ENSP00000461206.1	Q96E14-2
RMI2	ENST00000573910.1	TSL:3	n.160+23519C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

129871

AN:

152112

Hom.:

56196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.941

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.880

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.889

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.846

GnomAD2 exomes

AF:

0.868

AC:

127815

AN:

147212

AF XY:

0.872

show subpopulations

Gnomad AFR exome

AF:

0.762

Gnomad AMR exome

AF:

0.888

Gnomad ASJ exome

AF:

0.883

Gnomad EAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.911

Gnomad NFE exome

AF:

0.927

Gnomad OTH exome

AF:

0.863

GnomAD4 exome

AF:

0.907

AC:

1259098

AN:

1388832

Hom.:

575696

Cov.:

AF XY:

0.907

AC XY:

620502

AN XY:

684294

show subpopulations

African (AFR)

AF:

0.758

AC:

23845

AN:

31474

American (AMR)

AF:

0.881

AC:

31285

AN:

35518

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

22037

AN:

24972

East Asian (EAS)

AF:

0.440

AC:

15682

AN:

35620

South Asian (SAS)

AF:

0.894

AC:

70467

AN:

78846

European-Finnish (FIN)

AF:

0.911

AC:

39709

AN:

43588

Middle Eastern (MID)

AF:

0.821

AC:

4623

AN:

5632

European-Non Finnish (NFE)

AF:

0.931

AC:

1000905

AN:

1075440

Other (OTH)

AF:

0.875

AC:

50545

AN:

57742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

6617

13233

19850

26466

33083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21110

42220

63330

84440

105550

<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:

0.854

AC:

129967

AN:

152230

Hom.:

56236

Cov.:

AF XY:

0.850

AC XY:

63299

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.765

AC:

31776

AN:

41524

American (AMR)

AF:

0.844

AC:

12914

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.880

AC:

3054

AN:

3472

East Asian (EAS)

AF:

0.480

AC:

2477

AN:

5164

South Asian (SAS)

AF:

0.889

AC:

4290

AN:

4826

European-Finnish (FIN)

AF:

0.910

AC:

9660

AN:

10616

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.925

AC:

62921

AN:

68014

Other (OTH)

AF:

0.847

AC:

1788

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

912

1824

2735

3647

4559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.897

Hom.:

151032

Bravo

AF:

0.845

TwinsUK

AF:

0.932

AC:

3456

ALSPAC

AF:

0.931

AC:

3587

ESP6500AA

AF:

0.816

AC:

2962

ESP6500EA

AF:

0.939

AC:

6508

ExAC

AF:

0.838

AC:

23693

Asia WGS

AF:

0.720

AC:

2505

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.5

(source)

DANN

Benign

0.77

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.023

MetaRNN

Benign

8.7e-7

MetaSVM

Benign

-0.95

PhyloP100

0.43

PrimateAI

Benign

0.32

PROVEAN

Benign

3.8

REVEL

Benign

0.068

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.023

ClinPred

0.0078

GERP RS

1.2

PromoterAI

0.011

Neutral

(source)

gMVP

0.0029

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over