NM_138382.3:c.296+175A>G

Variant names:

• chrX-106901299-T-C
• rs7057398
• NM_138382.3:c.296+175A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138382.3(RIPPLY1):​c.296+175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 111,094 control chromosomes in the GnomAD database, including 8,055 homozygotes. There are 13,184 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.

• Frequency: Genomes: 𝑓 0.40 (8055 hom., 13184 hem., cov: 23)
• Consequence: RIPPLY1 NM_138382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPPLY1	NM_138382.3	MANE Select	c.296+175A>G		intron	N/A	NP_612391.1
	CLDN2	NM_001171092.1		c.-179+795T>C		intron	N/A	NP_001164563.1
	RIPPLY1	NM_001171706.2		c.156-391A>G		intron	N/A	NP_001165177.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPPLY1	ENST00000276173.5	TSL:1 MANE Select	c.296+175A>G		intron	N/A	ENSP00000276173.4
	CLDN2	ENST00000541806.6	TSL:1	c.-179+795T>C		intron	N/A	ENSP00000441283.1
	RIPPLY1	ENST00000411805.1	TSL:1	c.156-391A>G		intron	N/A	ENSP00000400539.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 44837 AN: 111043 Hom.: 8050 Cov.: 23

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.404 AC: 44908 AN: 111094 Hom.: 8055 Cov.: 23 AF XY: 0.396 AC XY: 13184 AN XY: 33334

African (AFR) AF: 0.711 AC: 21616 AN: 30414

American (AMR) AF: 0.291 AC: 3075 AN: 10582

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 508 AN: 2633

East Asian (EAS) AF: 0.401 AC: 1393 AN: 3475

South Asian (SAS) AF: 0.461 AC: 1188 AN: 2578

European-Finnish (FIN) AF: 0.306 AC: 1837 AN: 5994

Middle Eastern (MID) AF: 0.212 AC: 46 AN: 217

European-Non Finnish (NFE) AF: 0.276 AC: 14603 AN: 52984

Other (OTH) AF: 0.364 AC: 560 AN: 1537

Alfa AF: 0.329 Hom.: 21096

Bravo AF: 0.415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7057398; hg19: chrX-106144529; COSMIC: COSV52175035;