Genetic Variant RPRM:p.Ala26Gly (chr2-153478489-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019845.3(RPRM):c.77C>G(p.Ala26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RPRM
NM_019845.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08022079).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPRM	NM_019845.3	MANE Select	c.77C>G	p.Ala26Gly	missense	Exon 1 of 1	NP_062819.1	Q9NS64
GALNT13	NM_001422879.1		c.-239+127G>C		intron	N/A	NP_001409808.1
GALNT13	NM_001422880.1		c.-239+127G>C		intron	N/A	NP_001409809.1	Q8IUC8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPRM	ENST00000325926.4	TSL:6 MANE Select	c.77C>G	p.Ala26Gly	missense	Exon 1 of 1	ENSP00000314946.3	Q9NS64
ENSG00000227400	ENST00000424322.1	TSL:4	n.430-56526C>G		intron	N/A
ENSG00000301085	ENST00000776049.1		n.265+127G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459774

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111410

Other (OTH)

AF:

0.00

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.093

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.72

M_CAP

Benign

0.0074

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.24

REVEL

Benign

0.068

Sift

Benign

0.33

Sift4G

Benign

0.33

Polyphen

0.0090

Vest4

0.18

MutPred

0.30

Loss of helix (P = 0.0093)

MVP

0.082

MPC

0.82

ClinPred

0.11

GERP RS

4.1

PromoterAI

-0.072

Neutral

(source)

Varity_R

0.085

gMVP

0.72

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over