rs151012354
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_001040167.2(LFNG):c.672C>T(p.Tyr224=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000819 in 1,612,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000078 ( 0 hom. )
Consequence
LFNG
NM_001040167.2 synonymous
NM_001040167.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.65
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 7-2525504-C-T is Benign according to our data. Variant chr7-2525504-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LFNG | NM_001040167.2 | c.672C>T | p.Tyr224= | synonymous_variant | 4/8 | ENST00000222725.10 | NP_001035257.1 | |
LFNG | NM_001040168.2 | c.672C>T | p.Tyr224= | synonymous_variant | 4/8 | NP_001035258.1 | ||
LFNG | NM_001166355.2 | c.459C>T | p.Tyr153= | synonymous_variant | 5/9 | NP_001159827.1 | ||
LFNG | NM_002304.3 | c.285C>T | p.Tyr95= | synonymous_variant | 5/9 | NP_002295.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LFNG | ENST00000222725.10 | c.672C>T | p.Tyr224= | synonymous_variant | 4/8 | 5 | NM_001040167.2 | ENSP00000222725 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152266Hom.: 0 Cov.: 34
GnomAD3 genomes
AF:
AC:
18
AN:
152266
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000893 AC: 22AN: 246312Hom.: 0 AF XY: 0.0000968 AC XY: 13AN XY: 134254
GnomAD3 exomes
AF:
AC:
22
AN:
246312
Hom.:
AF XY:
AC XY:
13
AN XY:
134254
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000781 AC: 114AN: 1459948Hom.: 0 Cov.: 34 AF XY: 0.0000675 AC XY: 49AN XY: 726322
GnomAD4 exome
AF:
AC:
114
AN:
1459948
Hom.:
Cov.:
34
AF XY:
AC XY:
49
AN XY:
726322
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000118 AC: 18AN: 152384Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10AN XY: 74526
GnomAD4 genome
AF:
AC:
18
AN:
152384
Hom.:
Cov.:
34
AF XY:
AC XY:
10
AN XY:
74526
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spondylocostal dysostosis 3, autosomal recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at