Variant chr16-11281212-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002761.3(PRM1):c.27C>G(p.Ser9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

PRM1
NM_002761.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRM1	NM_002761.3 linkuse as main transcript	c.27C>G	p.Ser9Arg	missense_variant	1/2	ENST00000312511.4	NP_002752.1
LOC105371082	XR_933070.4 linkuse as main transcript	n.178+31434G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRM1	ENST00000312511.4 linkuse as main transcript	c.27C>G	p.Ser9Arg	missense_variant	1/2	1	NM_002761.3	ENSP00000310515	P1
RMI2	ENST00000572173.1 linkuse as main transcript	c.-515-14004G>C		intron_variant		1		ENSP00000461206		Q96E14-2
RMI2	ENST00000573910.1 linkuse as main transcript	n.160+31434G>C		intron_variant, non_coding_transcript_variant		3
RMI2	ENST00000649869.1 linkuse as main transcript	n.152+31434G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251356

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000270

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.27C>G (p.S9R) alteration is located in exon 1 (coding exon 1) of the PRM1 gene. This alteration results from a C to G substitution at nucleotide position 27, causing the serine (S) at amino acid position 9 to be replaced by an arginine (R). 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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.43

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.29

MutationTaster

Benign

0.60

N;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.17

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.43

MutPred

0.39

Loss of phosphorylation at S9 (P = 4e-04);

MVP

0.20

MPC

0.32

ClinPred

0.85

GERP RS

4.4

Varity_R

0.77

gMVP

0.0084

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over