Genetic Variant LFNG:c.-74C>T (chr7-2519788-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040167.2(LFNG):c.-74C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LFNG
NM_001040167.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

0 publications found

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]

LFNG Gene-Disease associations (from GenCC):

spondylocostal dysostosis 3, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LFNG links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LFNG	NM_001040167.2	MANE Select	c.-74C>T	5_prime_UTR	Exon 1 of 8	NP_001035257.1	Q8NES3-1
LFNG	NM_001040168.2		c.-74C>T	5_prime_UTR	Exon 1 of 8	NP_001035258.1	Q8NES3-3
LFNG	NM_001166355.2		c.220-4907C>T	intron	N/A	NP_001159827.1	Q8NES3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LFNG	ENST00000222725.10	TSL:5 MANE Select	c.-74C>T	5_prime_UTR	Exon 1 of 8	ENSP00000222725.5	Q8NES3-1
LFNG	ENST00000338732.7	TSL:1	c.45+1190C>T	intron	N/A	ENSP00000343095.3	Q8NES3-2
LFNG	ENST00000402045.5	TSL:1	c.45+1190C>T	intron	N/A	ENSP00000384786.1	Q8NES3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

751522

Hom.:

AF XY:

0.00

AC XY:

AN XY:

351250

African (AFR)

AF:

0.00

AC:

AN:

14098

American (AMR)

AF:

0.00

AC:

AN:

1456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5286

East Asian (EAS)

AF:

0.00

AC:

AN:

6038

South Asian (SAS)

AF:

0.00

AC:

AN:

14976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1600

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

679680

Other (OTH)

AF:

0.00

AC:

AN:

25266

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

-1.4

PromoterAI

-0.13

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over