NM_002917.2:c.640C>A

Variant names:

• chr17-82049940-G-T
• NM_002917.2:c.640C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002917.2(RFNG):​c.640C>A​(p.Leu214Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: RFNG NM_002917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFNG	NM_002917.2	c.640C>A	p.Leu214Ile	missense_variant	Exon 5 of 8	ENST00000310496.9	NP_002908.1
RFNG	XM_011523587.3	c.262C>A	p.Leu88Ile	missense_variant	Exon 4 of 7		XP_011521889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFNG	ENST00000310496.9	c.640C>A	p.Leu214Ile	missense_variant	Exon 5 of 8	2	NM_002917.2	ENSP00000307971.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.7	N;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.70		Gain of catalytic residue at L214 (P = 0.0836);.;
MVP		0.76
MPC		1.1
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.40

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: chr17-80007816;