NM_138382.3:c.331C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_138382.3(RIPPLY1):c.331C>T(p.Leu111Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,209,306 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00088 ( 0 hom., 30 hem., cov: 22)
Exomes 𝑓: 0.000095 ( 0 hom. 36 hem. )
Consequence
RIPPLY1
NM_138382.3 synonymous
NM_138382.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.27
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant X-106900874-G-A is Benign according to our data. Variant chrX-106900874-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052211.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=2.27 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 30 gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RIPPLY1 | NM_138382.3 | c.331C>T | p.Leu111Leu | synonymous_variant | Exon 4 of 4 | ENST00000276173.5 | NP_612391.1 | |
| RIPPLY1 | NM_001171706.2 | c.190C>T | p.Leu64Leu | synonymous_variant | Exon 2 of 2 | NP_001165177.1 | ||
| CLDN2 | NM_001171092.1 | c.-179+370G>A | intron_variant | Intron 1 of 1 | NP_001164563.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RIPPLY1 | ENST00000276173.5 | c.331C>T | p.Leu111Leu | synonymous_variant | Exon 4 of 4 | 1 | NM_138382.3 | ENSP00000276173.4 | ||
| RIPPLY1 | ENST00000411805.1 | c.190C>T | p.Leu64Leu | synonymous_variant | Exon 2 of 2 | 1 | ENSP00000400539.1 | |||
| CLDN2 | ENST00000541806.6 | c.-179+370G>A | intron_variant | Intron 1 of 1 | 1 | ENSP00000441283.1 | ||||
| MORC4 | ENST00000604604.1 | c.111-85088C>T | intron_variant | Intron 1 of 1 | 2 | ENSP00000474750.1 |
Frequencies
GnomAD3 genomes 0.000884 AC: 99AN: 111979Hom.: 0 Cov.: 22 AF XY: 0.000878 AC XY: 30AN XY: 34159
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GnomAD3 exomes AF: 0.000344 AC: 62AN: 180392Hom.: 0 AF XY: 0.000256 AC XY: 17AN XY: 66502
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GnomAD4 exome AF: 0.0000948 AC: 104AN: 1097274Hom.: 0 Cov.: 30 AF XY: 0.0000992 AC XY: 36AN XY: 362722
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GnomAD4 genome 0.000884 AC: 99AN: 112032Hom.: 0 Cov.: 22 AF XY: 0.000877 AC XY: 30AN XY: 34222
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
RIPPLY1-related disorder Benign:1
Mar 21, 2022
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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at