chr6-83853483-C-G

Variant names:

• chr6-83853483-C-G
• rs930754695
• NM_001009994.3:c.67C>G

Variant summary

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

The NM_001009994.3(RIPPLY2):​c.67C>G​(p.Pro23Ala) 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. 13/20 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: 33)
• Consequence: RIPPLY2 NM_001009994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

Genes affected

RIPPLY2 (HGNC:21390): (ripply transcriptional repressor 2) This gene encodes a nuclear protein that belongs to a novel family of proteins required for vertebrate somitogenesis. Members of this family have a tetrapeptide WRPW motif that is required for interaction with the transcriptional repressor Groucho and a carboxy-terminal Ripply homology domain/Bowline-DSCR-Ledgerline conserved region required for transcriptional repression. Null mutant mice die soon after birth and display defects in axial skeleton segmentation due to defective somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ENSG00000287705 (HGNC:):

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=0.084322006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPPLY2	NM_001009994.3	c.67C>G	p.Pro23Ala	missense_variant	Exon 1 of 4	ENST00000369689.6	NP_001009994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPPLY2	ENST00000369689.6	c.67C>G	p.Pro23Ala	missense_variant	Exon 1 of 4	1	NM_001009994.3	ENSP00000358703.1
ENSG00000287705	ENST00000656981.1	n.685G>C		non_coding_transcript_exon_variant	Exon 1 of 1
RIPPLY2	ENST00000369687.2	c.-291C>G		upstream_gene_variant		2		ENSP00000358701.1
RIPPLY2	ENST00000635617.1	n.-107C>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.36	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.022
Sift	Benign	0.053	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.17		Loss of loop (P = 0.0073);
MVP		0.18
MPC		0.15
ClinPred		0.087	T
GERP RS		0.57
Varity_R		0.036
gMVP		0.036

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

LitVar

Other links and lift over

dbSNP: rs930754695; hg19: chr6-84563202;