Genetic Variant NM_018962.3:c.94G>A (chr21-37006866-G-A) – 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_018962.3(RIPPLY3):c.94G>A(p.Gly32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,219,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

RIPPLY3
NM_018962.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.771

Publications

0 publications found

Variant links:

Genes affected

RIPPLY3 (HGNC:3047): (ripply transcriptional repressor 3) Predicted to be involved in embryonic pattern specification and negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of cell population proliferation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RIPPLY3 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=0.2227971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018962.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIPPLY3	NM_018962.3	MANE Select	c.94G>A	p.Gly32Arg	missense	Exon 1 of 4	NP_061835.1	P57055-1
RIPPLY3	NM_001317768.2		c.-149+633G>A		intron	N/A	NP_001304697.1	P57055-2
RIPPLY3	NM_001317777.1		c.-81+633G>A		intron	N/A	NP_001304706.1	P57055-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIPPLY3	ENST00000329553.3	TSL:1 MANE Select	c.94G>A	p.Gly32Arg	missense	Exon 1 of 4	ENSP00000331734.2	P57055-1
RIPPLY3	ENST00000485272.5	TSL:1	n.84+633G>A		intron	N/A
RIPPLY3	ENST00000490393.1	TSL:1	n.32+633G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000750

AC:

AN:

1067000

Hom.:

Cov.:

AF XY:

0.00000198

AC XY:

AN XY:

503798

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22378

American (AMR)

AF:

0.000252

AC:

AN:

7942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13736

East Asian (EAS)

AF:

0.00

AC:

AN:

25508

South Asian (SAS)

AF:

0.00

AC:

AN:

19440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2848

European-Non Finnish (NFE)

AF:

0.00000658

AC:

AN:

911554

Other (OTH)

AF:

0.00

AC:

AN:

42656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

AF:

0.0000197

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.24

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.10

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.51

M_CAP

Benign

0.036

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

PhyloP100

0.77

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.092

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.18

MutPred

0.14

Gain of solvent accessibility (P = 0.0456)

MVP

0.085

MPC

0.20

ClinPred

0.58

GERP RS

2.6

PromoterAI

0.14

Neutral

(source)

Varity_R

0.14

gMVP

0.066

Mutation Taster

=95/5

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

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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