Variant 16-67540089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024519.4(RIPOR1):c.451C>T(p.Arg151Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

RIPOR1
NM_024519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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:

RIPOR1 (HGNC:):

RIPOR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR1	NM_024519.4 linkuse as main transcript	c.451C>T	p.Arg151Cys	missense_variant	7/22	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.451C>T	p.Arg151Cys	missense_variant	7/22	5	NM_024519.4	ENSP00000042381.4		Q6ZS17-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152200

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251364

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135832

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727246

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:

0.0000116

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Feb 22, 2023

The c.511C>T (p.R171C) alteration is located in exon 7 (coding exon 7) of the FAM65A gene. This alteration results from a C to T substitution at nucleotide position 511, causing the arginine (R) at amino acid position 171 to be replaced by a cysteine (C). 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

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

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

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

1.0

D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.096

MetaRNN

Uncertain

0.73

D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-7.2

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

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

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

Vest4

0.76

MVP

0.72

MPC

1.8

ClinPred

0.96

GERP RS

3.0

Varity_R

0.91

gMVP

0.71

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

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