Genetic Variant NM_019845.3:c.77C>T (chr2-153478489-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019845.3(RPRM):c.77C>T(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,612,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

RPRM
NM_019845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008041561).

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>T	p.Ala26Val	missense	Exon 1 of 1	NP_062819.1	Q9NS64
GALNT13	NM_001422879.1		c.-239+127G>A		intron	N/A	NP_001409808.1
GALNT13	NM_001422880.1		c.-239+127G>A		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>T	p.Ala26Val	missense	Exon 1 of 1	ENSP00000314946.3	Q9NS64
ENSG00000227400	ENST00000424322.1	TSL:4	n.430-56526C>T		intron	N/A
ENSG00000301085	ENST00000776049.1		n.265+127G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000281

AC:

AN:

242266

AF XY:

0.000333

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00234

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000946

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.000168

AC:

245

AN:

1459774

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

726162

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33450

American (AMR)

AF:

0.0000448

AC:

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.00261

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.000929

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52436

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

1111410

Other (OTH)

AF:

0.000365

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000105

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41588

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00124

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

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:

0.000374

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000256

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.079

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.71

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

1.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.41

REVEL

Benign

0.097

Sift

Benign

0.82

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.082

MVP

0.043

MPC

0.81

ClinPred

0.019

GERP RS

4.1

PromoterAI

-0.00060

Neutral

(source)

Varity_R

0.061

gMVP

0.65

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over