Genetic Variant RFNG:p.Arg68Trp (chr17-82051565-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002917.2(RFNG):c.202C>T(p.Arg68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,388,086 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

RFNG
NM_002917.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Publications

0 publications found

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:

GPS1 (HGNC:4549): (G protein pathway suppressor 1) This gene is known to suppress G-protein and mitogen-activated signal transduction in mammalian cells. The encoded protein shares significant similarity with Arabidopsis FUS6, which is a regulator of light-mediated signal transduction in plant cells. [provided by RefSeq, Mar 2016]

GPS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0099128485).

BS2

High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFNG	NM_002917.2	MANE Select	c.202C>T	p.Arg68Trp	missense	Exon 1 of 8	NP_002908.1	Q9Y644
GPS1	NM_001394760.1		c.-52+41G>A		intron	N/A	NP_001381689.1
GPS1	NM_001394761.1		c.-52+41G>A		intron	N/A	NP_001381690.1	A8K070

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFNG	ENST00000310496.9	TSL:2 MANE Select	c.202C>T	p.Arg68Trp	missense	Exon 1 of 8	ENSP00000307971.4	Q9Y644
RFNG	ENST00000582478.5	TSL:1	n.267C>T		non_coding_transcript_exon	Exon 1 of 4
RFNG	ENST00000578356.1	TSL:5	c.-459C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000463623.1	J3QLN0

Frequencies

GnomAD3 genomes

AF:

0.0000794

AC:

AN:

151112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

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

GnomAD2 exomes

AF:

0.000962

AC:

AN:

58188

AF XY:

0.000783

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00615

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000641

GnomAD4 exome

AF:

0.0000695

AC:

AN:

1236974

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

608406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24800

American (AMR)

AF:

0.00359

AC:

AN:

18130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19614

East Asian (EAS)

AF:

0.00

AC:

AN:

26058

South Asian (SAS)

AF:

0.0000166

AC:

AN:

60356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3476

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

999376

Other (OTH)

AF:

0.0000404

AC:

AN:

49498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000794

AC:

AN:

151112

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

73808

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41262

American (AMR)

AF:

0.000724

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67696

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000264

ExAC

AF:

0.000305

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.0028

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.5

PhyloP100

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.25

Sift

Benign

0.091

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.28

MutPred

0.55

Loss of disorder (P = 0.0223)

MVP

0.56

MPC

1.1

ClinPred

0.14

GERP RS

-3.0

PromoterAI

-0.30

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.71

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over