NM_002917.2:c.730G>C

Variant names:

• chr17-82049775-C-G
• NM_002917.2:c.730G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002917.2(RFNG):​c.730G>C​(p.Val244Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000727 in 1,376,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RFNG NM_002917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38093492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFNG	NM_002917.2	c.730G>C	p.Val244Leu	missense_variant	Exon 6 of 8	ENST00000310496.9	NP_002908.1
RFNG	XM_011523587.3	c.352G>C	p.Val118Leu	missense_variant	Exon 5 of 7		XP_011521889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFNG	ENST00000310496.9	c.730G>C	p.Val244Leu	missense_variant	Exon 6 of 8	2	NM_002917.2	ENSP00000307971.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376042 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 676124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000177

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	0.0095
Eigen_PC	Benign	0.025
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.77	P;.
Vest4		0.20
MutPred		0.72		Loss of catalytic residue at V244 (P = 0.1182);.;
MVP		0.67
MPC		0.57
ClinPred		0.89	D
GERP RS		1.7
Varity_R		0.26
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80007651;