NM_018962.3:c.478G>T

Variant names:

• chr21-37018112-G-T
• NM_018962.3:c.478G>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.478G>T​(p.Gly160Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: RIPPLY3 NM_018962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.182
• 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=0.12066734).

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.478G>T	p.Gly160Trp	missense	Exon 4 of 4	NP_061835.1	P57055-1
	RIPPLY3	NM_001317768.2		c.226G>T	p.Gly76Trp	missense	Exon 4 of 4	NP_001304697.1	P57055-2
	RIPPLY3	NM_001317777.1		c.226G>T	p.Gly76Trp	missense	Exon 3 of 3	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.478G>T	p.Gly160Trp	missense	Exon 4 of 4	ENSP00000331734.2	P57055-1
	RIPPLY3	ENST00000485272.5	TSL:1	n.458G>T		non_coding_transcript_exon	Exon 4 of 4
	RIPPLY3	ENST00000490393.1	TSL:1	n.338G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.18
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.070
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.18		Gain of sheet (P = 0.0149)
MVP		0.040
MPC		0.41
ClinPred		0.41	T
GERP RS		-1.2
Varity_R		0.10
gMVP		0.060
Mutation Taster		=98/2	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

hg19: chr21-38390412;