Variant chr2-153478403-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019845.3(RPRM):c.163C>A(p.Arg55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

RPRM
NM_019845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

RPRM (HGNC:24201): (reprimo, TP53 dependent G2 arrest mediator homolog) Predicted to be involved in regulation of mitotic cell cycle. Predicted to act upstream of or within regulation of cell cycle. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RPRM links:

GALNT13 (HGNC:23242): (polypeptide N-acetylgalactosaminyltransferase 13) The GALNT13 protein is a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAcT; EC 2.4.1.41) family, which initiate O-linked glycosylation of mucins (see MUC3A, MIM 158371) by the initial transfer of N-acetylgalactosamine (GalNAc) with an alpha-linkage to a serine or threonine residue.[supplied by OMIM, Apr 2004]

GALNT13 links:

ENSG00000227400 (HGNC:):

ENSG00000227400 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRM	NM_019845.3 linkuse as main transcript	c.163C>A	p.Arg55Ser	missense_variant	1/1	ENST00000325926.4	NP_062819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRM	ENST00000325926.4 linkuse as main transcript	c.163C>A	p.Arg55Ser	missense_variant	1/1	6	NM_019845.3	ENSP00000314946.3		Q9NS64
ENSG00000227400	ENST00000424322.1 linkuse as main transcript	n.430-56440C>A		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251140

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135860

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727220

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

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

Nov 08, 2024

The c.163C>A (p.R55S) alteration is located in exon 1 (coding exon 1) of the RPRM gene. This alteration results from a C to A substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a serine (S). 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

0.90

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.80

MetaSVM

Uncertain

-0.083

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.86

MutPred

0.59

Loss of sheet (P = 0.0357);

MVP

0.50

MPC

1.9

ClinPred

0.99

GERP RS

5.0

Varity_R

0.97

gMVP

0.91

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