rs2069485312

Variant names:

• chr21-37008216-G-A
• NM_018962.3:c.164G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-37008216-G-A
• chr21-37008216-G-C
• chr21-37008216-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018962.3(RIPPLY3):​c.164G>A​(p.Gly55Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RIPPLY3 NM_018962.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060340554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPPLY3	NM_018962.3	c.164G>A	p.Gly55Glu	missense_variant	Exon 2 of 4	ENST00000329553.3	NP_061835.1
RIPPLY3	NM_001317768.2	c.-89G>A		5_prime_UTR_variant	Exon 2 of 4		NP_001304697.1
RIPPLY3	NM_001317777.1	c.-21G>A		5_prime_UTR_variant	Exon 2 of 3		NP_001304706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPPLY3	ENST00000329553.3	c.164G>A	p.Gly55Glu	missense_variant	Exon 2 of 4	1	NM_018962.3	ENSP00000331734.2
RIPPLY3	ENST00000485272.5	n.144G>A		non_coding_transcript_exon_variant	Exon 2 of 4	1
RIPPLY3	ENST00000490393.1	n.92G>A		non_coding_transcript_exon_variant	Exon 2 of 3	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Benign	0.57
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.023
Sift	Benign	0.35	T
Sift4G	Benign	0.95	T
Polyphen		0.087	B
Vest4		0.26
MutPred		0.12		Gain of solvent accessibility (P = 0.0456);
MVP		0.13
MPC		0.085
ClinPred		0.087	T
GERP RS		1.8
Varity_R		0.042
gMVP		0.062

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-38380516;