rs925641455

Variant names:

• chr21-37006800-C-G
• rs925641455
• NM_018962.3:c.28C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-37006800-C-G
• chr21-37006800-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018962.3(RIPPLY3):​c.28C>G​(p.Arg10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,232,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: RIPPLY3 NM_018962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.428
• Publications: 0 publications found

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]

ACMG classification

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=0.09467268).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPPLY3	NM_018962.3	MANE Select	c.28C>G	p.Arg10Gly	missense	Exon 1 of 4	NP_061835.1	P57055-1
	RIPPLY3	NM_001317768.2		c.-149+567C>G		intron	N/A	NP_001304697.1	P57055-2
	RIPPLY3	NM_001317777.1		c.-81+567C>G		intron	N/A	NP_001304706.1	P57055-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPPLY3	ENST00000329553.3	TSL:1 MANE Select	c.28C>G	p.Arg10Gly	missense	Exon 1 of 4	ENSP00000331734.2	P57055-1
	RIPPLY3	ENST00000485272.5	TSL:1	n.84+567C>G		intron	N/A
	RIPPLY3	ENST00000490393.1	TSL:1	n.32+567C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000555 AC: 6 AN: 1080712 Hom.: 0 Cov.: 30 AF XY: 0.00000586 AC XY: 3 AN XY: 512276

African (AFR) AF: 0.000221 AC: 5 AN: 22600

American (AMR) AF: 0.00 AC: 0 AN: 8246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14054

East Asian (EAS) AF: 0.00 AC: 0 AN: 26060

South Asian (SAS) AF: 0.00 AC: 0 AN: 21338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920878

Other (OTH) AF: 0.0000231 AC: 1 AN: 43306

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152060 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74282

African (AFR) AF: 0.000169 AC: 7 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.78
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.43
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.045
Sift	Benign	0.10	T
Sift4G	Benign	0.64	T
Polyphen		0.28	B
Vest4		0.14
MutPred		0.21		Gain of loop (P = 0.0045)
MVP		0.31
MPC		0.087
ClinPred		0.15	T
GERP RS		2.5
PromoterAI		-0.25	Neutral
Varity_R		0.10
gMVP		0.24
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs925641455; hg19: chr21-38379100;