Variant chr16-67538716-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024519.4(RIPOR1):c.149C>T(p.Pro50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RIPOR1
NM_024519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.934

Variant links:

Genes affected

RIPOR1 (HGNC:25836): (RHO family interacting cell polarization regulator 1) Enables 14-3-3 protein binding activity. Involved in several processes, including establishment of Golgi localization; negative regulation of Rho guanyl-nucleotide exchange factor activity; and negative regulation of Rho protein signal transduction. Located in Golgi apparatus; cell leading edge; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

RIPOR1 links:

ENSG00000261396 (HGNC:):

ENSG00000261396 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07283202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR1	NM_024519.4 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	3/22	ENST00000042381.9	NP_078795.2	Q6ZS17-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR1	ENST00000042381.9 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	3/22	5	NM_024519.4	ENSP00000042381.4		Q6ZS17-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245802

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461070

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.209C>T (p.P70L) alteration is located in exon 3 (coding exon 3) of the FAM65A gene. This alteration results from a C to T substitution at nucleotide position 209, causing the proline (P) at amino acid position 70 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;T;.;T;.;.;.;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.82

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.073

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.6

D;.;D;.;D;D;.;D;D

REVEL

Benign

0.046

Sift

Benign

0.21

T;.;T;.;T;T;.;D;T

Sift4G

Benign

0.29

T;T;T;T;T;T;T;T;T

Polyphen

0.0020

.;B;.;.;.;.;.;.;.

Vest4

0.24, 0.21, 0.28, 0.29

MutPred

0.16

.;Loss of catalytic residue at P53 (P = 0.0193);.;.;.;.;.;.;.;

MVP

0.068

MPC

0.62

ClinPred

0.25

GERP RS

2.9

Varity_R

0.039

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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