dbSNP rs35262993: PRM1:p.Gln18Gln (chr16-11281185-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_002761.3(PRM1):c.54G>A(p.Gln18Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,614,198 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 15 hom. )

Consequence

PRM1
NM_002761.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

7 publications found

Variant links:

Genes affected

PRM1 (HGNC:9447): (protamine 1) Predicted to enable DNA binding activity. Predicted to be involved in DNA packaging. Predicted to act upstream of or within nucleus organization and spermatid development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRM1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00213 (3115/1461860) while in subpopulation MID AF = 0.0218 (126/5768). AF 95% confidence interval is 0.0187. There are 15 homozygotes in GnomAdExome4. There are 1593 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRM1	NM_002761.3 link	c.54G>A	p.Gln18Gln	synonymous_variant	Exon 1 of 2	ENST00000312511.4	NP_002752.1	P04553Q3MN80
LOC105371082	XR_933070.4 link	n.178+31407C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRM1	ENST00000312511.4 link	c.54G>A	p.Gln18Gln	synonymous_variant	Exon 1 of 2	1	NM_002761.3	ENSP00000310515.3	P04553
RMI2	ENST00000572173.1 link	c.-515-14031C>T		intron_variant	Intron 1 of 4	1		ENSP00000461206.1	Q96E14-2
RMI2	ENST00000573910.1 link	n.160+31407C>T		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1 link	n.152+31407C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

867

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00311

AC:

782

AN:

251438

AF XY:

0.00280

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00192

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00213

AC:

3115

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1593

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0161

AC:

539

AN:

33478

American (AMR)

AF:

0.00282

AC:

126

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

182

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00293

AC:

253

AN:

86258

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.0218

AC:

126

AN:

5768

European-Non Finnish (NFE)

AF:

0.00148

AC:

1649

AN:

1112010

Other (OTH)

AF:

0.00374

AC:

226

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

210

420

629

839

1049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00569

AC:

867

AN:

152338

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0159

AC:

662

AN:

41562

American (AMR)

AF:

0.00288

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00163

AC:

111

AN:

68038

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00453

Hom.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

(source)

DANN

Benign

0.70

PhyloP100

-1.1

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over