7-2519936-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001040167.2(LFNG):c.75C>T(p.Thr25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,025,050 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0022 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 9 hom. )
Consequence
LFNG
NM_001040167.2 synonymous
NM_001040167.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.892
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 Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 7-2519936-C-T is Benign according to our data. Variant chr7-2519936-C-T is described in ClinVar as [Benign]. Clinvar id is 1165699.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.892 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LFNG | NM_001040167.2 | c.75C>T | p.Thr25= | synonymous_variant | 1/8 | ENST00000222725.10 | NP_001035257.1 | |
LFNG | NM_001040168.2 | c.75C>T | p.Thr25= | synonymous_variant | 1/8 | NP_001035258.1 | ||
LFNG | NM_001166355.2 | c.220-4759C>T | intron_variant | NP_001159827.1 | ||||
LFNG | NM_002304.3 | c.45+1338C>T | intron_variant | NP_002295.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LFNG | ENST00000222725.10 | c.75C>T | p.Thr25= | synonymous_variant | 1/8 | 5 | NM_001040167.2 | ENSP00000222725 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00218 AC: 318AN: 145562Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00882 AC: 15AN: 1700Hom.: 0 AF XY: 0.00963 AC XY: 11AN XY: 1142
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GnomAD4 exome AF: 0.00285 AC: 2502AN: 879396Hom.: 9 Cov.: 30 AF XY: 0.00290 AC XY: 1192AN XY: 411358
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GnomAD4 genome AF: 0.00218 AC: 318AN: 145654Hom.: 4 Cov.: 32 AF XY: 0.00206 AC XY: 146AN XY: 70906
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spondylocostal dysostosis 3, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
LFNG-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 22, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at