Variant 20-50594624-G-A 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_001290268.2(RIPOR3):c.2141C>T(p.Thr714Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,846 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

RIPOR3
NM_001290268.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.415

Variant links:

Genes affected

RIPOR3 (HGNC:16168): (RIPOR family member 3)

RIPOR3 links:

Genome browser will be placed here

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=0.1222727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR3	NM_001290268.2 linkuse as main transcript	c.2141C>T	p.Thr714Met	missense_variant	17/22	ENST00000327979.8	NP_001277197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR3	ENST00000327979.8 linkuse as main transcript	c.2141C>T	p.Thr714Met	missense_variant	17/22	2	NM_001290268.2	ENSP00000332663
RIPOR3	ENST00000045083.6 linkuse as main transcript	c.2129C>T	p.Thr710Met	missense_variant	17/22	5		ENSP00000045083	P1	Q96MK2-1
RIPOR3	ENST00000482129.1 linkuse as main transcript	n.569C>T		non_coding_transcript_exon_variant	1/3	3
RIPOR3	ENST00000488529.5 linkuse as main transcript	n.464C>T		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000762

AC:

AN:

249482

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000164

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000522

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000506

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 16, 2023

The c.2129C>T (p.T710M) alteration is located in exon 17 (coding exon 16) of the FAM65C gene. This alteration results from a C to T substitution at nucleotide position 2129, causing the threonine (T) at amino acid position 710 to be replaced by a methionine (M). 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

0.087

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.2

DANN

Benign

0.87

DEOGEN2

Benign

0.033

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.68

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.59

N;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.041

D;D

Polyphen

0.94

P;P

Vest4

0.11

MVP

0.21

MPC

0.11

ClinPred

0.020

GERP RS

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.21

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