X-106902183-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_138382.3(RIPPLY1):c.188C>A(p.Ser63Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,189,761 control chromosomes in the GnomAD database, including 1 homozygotes. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 1 hom. 50 hem. )

Consequence

RIPPLY1
NM_138382.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

RIPPLY1 (HGNC:25117): (ripply transcriptional repressor 1) This gene encodes a protein similar to a zebrafish protein which acts as a transcriptional repressor in and is required for somite segmentation in zebrafish embryos (PMID: 16326386). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

RIPPLY1 links:

CLDN2 (HGNC:2041): (claudin 2) This gene product belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. This protein is expressed in the intestine. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene.[provided by RefSeq, Jan 2010]

CLDN2 links:

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

MORC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009198695).

BP6

Variant X-106902183-G-T is Benign according to our data. Variant chrX-106902183-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045265.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPPLY1	NM_138382.3 link	c.188C>A	p.Ser63Tyr	missense_variant	Exon 2 of 4	ENST00000276173.5	NP_612391.1	Q0D2K3-1
CLDN2	NM_001171092.1 link	c.-179+1679G>T		intron_variant	Intron 1 of 1		NP_001164563.1	P57739
RIPPLY1	NM_001171706.2 link	c.155+950C>A		intron_variant	Intron 1 of 1		NP_001165177.1	Q0D2K3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RIPPLY1	ENST00000276173.5 link	c.188C>A	p.Ser63Tyr	missense_variant	Exon 2 of 4	1	NM_138382.3	ENSP00000276173.4	Q0D2K3-1
CLDN2	ENST00000541806.6 link	c.-179+1679G>T		intron_variant	Intron 1 of 1	1		ENSP00000441283.1	P57739
RIPPLY1	ENST00000411805.1 link	c.155+950C>A		intron_variant	Intron 1 of 1	1		ENSP00000400539.1	Q0D2K3-2
MORC4	ENST00000604604.1 link	c.111-86397C>A		intron_variant	Intron 1 of 1	2		ENSP00000474750.1	S4R3U3

Frequencies

GnomAD3 genomes

AF:

0.0000898

AC:

AN:

111406

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33584

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000951

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00198

Gnomad SAS

AF:

0.000770

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000319

AC:

AN:

147251

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

45659

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00201

Gnomad SAS exome

AF:

0.00162

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

124

AN:

1078300

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

350606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000352

GnomAD4 genome

AF:

0.0000987

AC:

AN:

111461

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33649

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00227

Gnomad4 SAS

AF:

0.000772

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000346

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RIPPLY1-related disorder

Benign:1

Apr 11, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.62

M_CAP

Benign

0.033

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.23

Sift

Uncertain

0.011

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.061

MutPred

0.32

Loss of disorder (P = 0.0037);

MVP

0.24

MPC

0.24

ClinPred

0.086

GERP RS

4.3

Varity_R

0.23

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over