Variant chr16-11281141-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002761.3(PRM1):c.98G>T(p.Arg33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PRM1
NM_002761.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0610

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3448435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRM1	NM_002761.3 linkuse as main transcript	c.98G>T	p.Arg33Leu	missense_variant	1/2	ENST00000312511.4	NP_002752.1
LOC105371082	XR_933070.4 linkuse as main transcript	n.178+31363C>A		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.98G>T	p.Arg33Leu	missense_variant	1/2	1	NM_002761.3	ENSP00000310515	P1
RMI2	ENST00000572173.1 linkuse as main transcript	c.-515-14075C>A		intron_variant		1		ENSP00000461206		Q96E14-2
RMI2	ENST00000573910.1 linkuse as main transcript	n.160+31363C>A		intron_variant, non_coding_transcript_variant		3
RMI2	ENST00000649869.1 linkuse as main transcript	n.152+31363C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251432

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135894

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

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

Jan 17, 2024

The c.98G>T (p.R33L) alteration is located in exon 1 (coding exon 1) of the PRM1 gene. This alteration results from a G to T substitution at nucleotide position 98, causing the arginine (R) at amino acid position 33 to be replaced by a leucine (L). 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

0.26

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.5

DANN

Benign

0.80

DEOGEN2

Uncertain

0.54

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.066

M_CAP

Benign

0.0069

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.048

Sift4G

Uncertain

0.0030

Polyphen

0.98

Vest4

0.44

MVP

0.081

MPC

0.35

ClinPred

0.28

GERP RS

1.5

Varity_R

0.43

gMVP

0.018

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