rs560562511

Variant names:

• chrX-106902183-G-A
• rs560562511
• NM_138382.3:c.188C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-106902183-G-A
• chrX-106902183-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138382.3(RIPPLY1):​c.188C>T​(p.Ser63Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,078,299 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S63Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
• Consequence: RIPPLY1 NM_138382.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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]

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30648637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138382.3. 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
	RIPPLY1	NM_138382.3	MANE Select	c.188C>T	p.Ser63Phe	missense	Exon 2 of 4	NP_612391.1	Q0D2K3-1
	CLDN2	NM_001171092.1		c.-179+1679G>A		intron	N/A	NP_001164563.1	P57739
	RIPPLY1	NM_001171706.2		c.155+950C>T		intron	N/A	NP_001165177.1	Q0D2K3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPPLY1	ENST00000276173.5	TSL:1 MANE Select	c.188C>T	p.Ser63Phe	missense	Exon 2 of 4	ENSP00000276173.4	Q0D2K3-1
	CLDN2	ENST00000541806.6	TSL:1	c.-179+1679G>A		intron	N/A	ENSP00000441283.1	P57739
	RIPPLY1	ENST00000411805.1	TSL:1	c.155+950C>T		intron	N/A	ENSP00000400539.1	Q0D2K3-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.27e-7 AC: 1 AN: 1078299 Hom.: 0 Cov.: 29 AF XY: 0.00000285 AC XY: 1 AN XY: 350605

African (AFR) AF: 0.00 AC: 0 AN: 25902

American (AMR) AF: 0.00 AC: 0 AN: 32623

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18990

East Asian (EAS) AF: 0.00 AC: 0 AN: 29109

South Asian (SAS) AF: 0.0000196 AC: 1 AN: 51119

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4079

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831738

Other (OTH) AF: 0.00 AC: 0 AN: 45417

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.00025	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.30		Loss of disorder (P = 0.0045)
MVP		0.24
MPC		0.23
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.23
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

dbSNP: rs560562511; hg19: chrX-106145413;