7-2525553-AGC-TCG

Variant names:

• chr7-2525553-AGC-TCG
• NM_001040167.2:c.721_723delAGCinsTCG
• LFNG p.242

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040167.2(LFNG):​c.721_723delAGCinsTCG​(p.242) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S241S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LFNG NM_001040167.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• Publications: 0 publications found

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]

LFNG Gene-Disease associations (from GenCC):

• spondylocostal dysostosis 3, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040167.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LFNG	NM_001040167.2	MANE Select	c.721_723delAGCinsTCG	p.242	synonymous	N/A	NP_001035257.1	Q8NES3-1
	LFNG	NM_001040168.2		c.721_723delAGCinsTCG	p.242	synonymous	N/A	NP_001035258.1	Q8NES3-3
	LFNG	NM_001166355.2		c.508_510delAGCinsTCG	p.171	synonymous	N/A	NP_001159827.1	Q8NES3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LFNG	ENST00000222725.10	TSL:5 MANE Select	c.721_723delAGCinsTCG	p.242	synonymous	N/A	ENSP00000222725.5	Q8NES3-1
	LFNG	ENST00000359574.7	TSL:1	c.721_723delAGCinsTCG	p.242	synonymous	N/A	ENSP00000352579.3	Q8NES3-3
	LFNG	ENST00000338732.7	TSL:1	c.334_336delAGCinsTCG	p.113	synonymous	N/A	ENSP00000343095.3	Q8NES3-2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-2565187;