Variant 16-67538691-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024519.4(RIPOR1):c.124C>T(p.Pro42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,612,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

RIPOR1
NM_024519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042946517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR1	NM_024519.4 link	c.124C>T	p.Pro42Ser	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 link	c.124C>T	p.Pro42Ser	missense_variant	3/22	5	NM_024519.4	ENSP00000042381.4		Q6ZS17-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000236

AC:

AN:

245666

Hom.:

AF XY:

0.000261

AC XY:

AN XY:

134110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.000364

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.000199

AC:

290

AN:

1460770

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

726692

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000816

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000171

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000237

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.000315

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Aug 11, 2022

The c.184C>T (p.P62S) 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 184, causing the proline (P) at amino acid position 62 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0014

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

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

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

M_CAP

Benign

0.0069

MetaRNN

Benign

0.043

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

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

N;D;N;.;N;N;.;.;N

REVEL

Benign

0.056

Sift

Benign

0.37

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

Sift4G

Benign

0.30

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

Polyphen

0.022

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

Vest4

0.38, 0.35, 0.32, 0.36, 0.39

MVP

0.068

MPC

0.71

ClinPred

0.055

GERP RS

4.3

Varity_R

0.074

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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