17-82050728-C-A

Variant names:

• chr17-82050728-C-A
• rs762755184
• NM_002917.2:c.353G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_002917.2(RFNG):​c.353G>T​(p.Arg118Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,460,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R118H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: RFNG NM_002917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888
• BS2: High AC in GnomAdExome4 at 11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFNG	NM_002917.2	MANE Select	c.353G>T	p.Arg118Leu	missense	Exon 3 of 8	NP_002908.1	Q9Y644
	GPS1	NM_001394765.1		c.-379C>A		upstream_gene	N/A	NP_001381694.1
	GPS1	NM_001394769.1		c.-379C>A		upstream_gene	N/A	NP_001381698.1	C9JFE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFNG	ENST00000310496.9	TSL:2 MANE Select	c.353G>T	p.Arg118Leu	missense	Exon 3 of 8	ENSP00000307971.4	Q9Y644
	RFNG	ENST00000582478.5	TSL:1	n.947G>T		non_coding_transcript_exon	Exon 2 of 4
	RFNG	ENST00000901399.1		c.353G>T	p.Arg118Leu	missense	Exon 3 of 8	ENSP00000571458.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460822 Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4 AN XY: 726726

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111916

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.5
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.85	P
Vest4		0.58
MutPred		0.78		Gain of stability (P = 0.0742)
MVP		0.64
MPC		0.86
ClinPred		0.95	D
GERP RS		1.4
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.54
Mutation Taster		=265/35	polymorphism

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

Other links and lift over

dbSNP: rs762755184; hg19: chr17-80008604;