17-82049948-C-T

Variant names:

• chr17-82049948-C-T
• rs754177910
• NM_002917.2:c.632G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002917.2(RFNG):​c.632G>A​(p.Gly211Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,270 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.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RFNG NM_002917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFNG	NM_002917.2	c.632G>A	p.Gly211Asp	missense_variant	Exon 5 of 8	ENST00000310496.9	NP_002908.1
RFNG	XM_011523587.3	c.254G>A	p.Gly85Asp	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.632G>A	p.Gly211Asp	missense_variant	Exon 5 of 8	2	NM_002917.2	ENSP00000307971.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247708 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134586

Gnomad AFR exome AF: 0.00

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: 0.000166

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460270 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726390

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	-0.025	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.7	D;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.014	D;.
Sift4G	Uncertain	0.041	D;T
Polyphen		1.0	D;.
Vest4		0.92
MutPred		0.65		Loss of methylation at R210 (P = 0.0583);.;
MVP		0.88
MPC		1.2
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.77
gMVP		0.88

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

Other links and lift over

dbSNP: rs754177910; hg19: chr17-80007824;