Variant 17-82049086-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002917.2(RFNG):c.859C>G(p.Pro287Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RFNG
NM_002917.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Variant links:

Genes affected

RFNG (HGNC:9974): (RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) Predicted to enable O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity. Predicted to be involved in regulation of Notch signaling pathway. Predicted to act upstream of or within positive regulation of Notch signaling pathway and positive regulation of protein binding activity. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

RFNG links:

RFNG (HGNC:):

RFNG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19866648).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFNG	NM_002917.2 linkuse as main transcript	c.859C>G	p.Pro287Ala	missense_variant	7/8	ENST00000310496.9	NP_002908.1	Q9Y644Q8N9R1
RFNG	XM_011523587.3 linkuse as main transcript	c.481C>G	p.Pro161Ala	missense_variant	6/7		XP_011521889.1	F5H3H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFNG	ENST00000310496.9 linkuse as main transcript	c.859C>G	p.Pro287Ala	missense_variant	7/8	2	NM_002917.2	ENSP00000307971.4		Q9Y644

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250348

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.000556

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000125

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Jul 26, 2021

The c.859C>G (p.P287A) alteration is located in exon 7 (coding exon 7) of the RFNG gene. This alteration results from a C to G substitution at nucleotide position 859, causing the proline (P) at amino acid position 287 to be replaced by an alanine (A). 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

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.57

N;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.34

N;.

REVEL

Benign

0.11

Sift

Benign

0.072

T;.

Sift4G

Benign

0.18

T;T

Polyphen

0.54

P;.

Vest4

0.49

MVP

0.48

MPC

0.73

ClinPred

0.11

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.46

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