rs148460430

Variant summary

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

The NM_001040167.2(LFNG):​c.653C>A​(p.Pro218Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 34)

Consequence

LFNG
NM_001040167.2 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34
Variant links:
Genes affected
LFNG (HGNC:6560): (LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) This gene is a member of the glycosyltransferase 31 gene family. Members of this gene family, which also includes the MFNG (GeneID: 4242) and RFNG (GeneID: 5986) genes, encode evolutionarily conserved glycosyltransferases that act in the Notch signaling pathway to define boundaries during embryonic development. While their genomic structure is distinct from other glycosyltransferases, these proteins have a fucose-specific beta-1,3-N-acetylglucosaminyltransferase activity that leads to elongation of O-linked fucose residues on Notch, which alters Notch signaling. The protein encoded by this gene is predicted to be a single-pass type II Golgi membrane protein but it may also be secreted and proteolytically processed like the related proteins in mouse and Drosophila (PMID: 9187150). Mutations in this gene have been associated with autosomal recessive spondylocostal dysostosis 3. [provided by RefSeq, May 2018]

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ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
LFNGNM_001040167.2 linkuse as main transcriptc.653C>A p.Pro218Gln missense_variant 4/8 ENST00000222725.10 NP_001035257.1 Q8NES3-1
LFNGNM_001040168.2 linkuse as main transcriptc.653C>A p.Pro218Gln missense_variant 4/8 NP_001035258.1 Q8NES3-3
LFNGNM_001166355.2 linkuse as main transcriptc.440C>A p.Pro147Gln missense_variant 5/9 NP_001159827.1 Q8NES3-4
LFNGNM_002304.3 linkuse as main transcriptc.266C>A p.Pro89Gln missense_variant 5/9 NP_002295.1 Q8NES3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LFNGENST00000222725.10 linkuse as main transcriptc.653C>A p.Pro218Gln missense_variant 4/85 NM_001040167.2 ENSP00000222725.5 Q8NES3-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
.;.;.;T;.;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.83
T;.;T;T;T;T
M_CAP
Benign
0.076
D
MetaRNN
Uncertain
0.51
D;D;D;D;D;D
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.5
.;.;.;M;M;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;.
REVEL
Uncertain
0.37
Sift
Benign
0.036
D;D;D;D;D;.
Sift4G
Benign
0.075
T;T;T;T;T;T
Polyphen
0.99, 0.99
.;.;.;D;D;.
Vest4
0.49
MutPred
0.57
.;.;.;Loss of phosphorylation at T220 (P = 0.114);Loss of phosphorylation at T220 (P = 0.114);.;
MVP
0.79
MPC
0.70
ClinPred
0.98
D
GERP RS
4.2
Varity_R
0.21
gMVP
0.80

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148460430; hg19: chr7-2565119; COSMIC: COSV99761850; COSMIC: COSV99761850; API