NM_138382.3:c.285T>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138382.3(RIPPLY1):c.285T>A(p.His95Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,609 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

RIPPLY1
NM_138382.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11326647).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIPPLY1	NM_138382.3	MANE Select	c.285T>A	p.His95Gln	missense	Exon 3 of 4	NP_612391.1	Q0D2K3-1
CLDN2	NM_001171092.1		c.-179+981A>T		intron	N/A	NP_001164563.1	P57739
RIPPLY1	NM_001171706.2		c.156-577T>A		intron	N/A	NP_001165177.1	Q0D2K3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIPPLY1	ENST00000276173.5	TSL:1 MANE Select	c.285T>A	p.His95Gln	missense	Exon 3 of 4	ENSP00000276173.4	Q0D2K3-1
CLDN2	ENST00000541806.6	TSL:1	c.-179+981A>T		intron	N/A	ENSP00000441283.1	P57739
RIPPLY1	ENST00000411805.1	TSL:1	c.156-577T>A		intron	N/A	ENSP00000400539.1	Q0D2K3-2

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000276

AC:

AN:

180914

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000369

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097529

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362977

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26390

American (AMR)

AF:

0.00

AC:

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19378

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

54066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841597

Other (OTH)

AF:

0.00

AC:

AN:

46056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30876

American (AMR)

AF:

0.00

AC:

AN:

10620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.000282

AC:

AN:

3546

South Asian (SAS)

AF:

0.00

AC:

AN:

2679

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6101

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53178

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.092

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.51

M_CAP

Benign

0.0077

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PhyloP100

0.27

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.8

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.89

Polyphen

0.94

Vest4

0.26

MutPred

0.23

Gain of catalytic residue at H95 (P = 0.0388)

MVP

0.73

MPC

0.11

ClinPred

0.17

GERP RS

1.6

Varity_R

0.082

gMVP

0.099

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over