21-37017981-C-T

Variant names:

• chr21-37017981-C-T
• NM_018962.3:c.347C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018962.3(RIPPLY3):​c.347C>T​(p.Ser116Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 6.8e-7 (0 hom.)
• Consequence: RIPPLY3 NM_018962.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20671326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPPLY3	NM_018962.3	c.347C>T	p.Ser116Phe	missense_variant	Exon 4 of 4	ENST00000329553.3	NP_061835.1
RIPPLY3	NM_001317768.2	c.95C>T	p.Ser32Phe	missense_variant	Exon 4 of 4		NP_001304697.1
RIPPLY3	NM_001317777.1	c.95C>T	p.Ser32Phe	missense_variant	Exon 3 of 3		NP_001304706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPPLY3	ENST00000329553.3	c.347C>T	p.Ser116Phe	missense_variant	Exon 4 of 4	1	NM_018962.3	ENSP00000331734.2
RIPPLY3	ENST00000485272.5	n.327C>T		non_coding_transcript_exon_variant	Exon 4 of 4	1
RIPPLY3	ENST00000490393.1	n.207C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 8.99e-7

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	0.32
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.17		Loss of phosphorylation at S116 (P = 0.0088);
MVP		0.13
MPC		0.12
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.32
gMVP		0.046

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-38390281;