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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.65
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 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
LFNGNM_001040167.2 linkuse as main transcriptc.672C>T p.Tyr224= synonymous_variant 4/8 ENST00000222725.10 NP_001035257.1
LFNGNM_001040168.2 linkuse as main transcriptc.672C>T p.Tyr224= synonymous_variant 4/8 NP_001035258.1
LFNGNM_001166355.2 linkuse as main transcriptc.459C>T p.Tyr153= synonymous_variant 5/9 NP_001159827.1
LFNGNM_002304.3 linkuse as main transcriptc.285C>T p.Tyr95= synonymous_variant 5/9 NP_002295.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LFNGENST00000222725.10 linkuse as main transcriptc.672C>T p.Tyr224= synonymous_variant 4/85 NM_001040167.2 ENSP00000222725 P1Q8NES3-1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152266
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000893
AC:
22
AN:
246312
Hom.:
0
AF XY:
0.0000968
AC XY:
13
AN XY:
134254
show subpopulations
Gnomad AFR exome
AF:
0.0000641
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000117
Gnomad OTH exome
AF:
0.000333
GnomAD4 exome
AF:
0.0000781
AC:
114
AN:
1459948
Hom.:
0
Cov.:
34
AF XY:
0.0000675
AC XY:
49
AN XY:
726322
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000269
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000791
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152384
Hom.:
0
Cov.:
34
AF XY:
0.000134
AC XY:
10
AN XY:
74526
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.000295
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
13
DANN
Benign
0.88

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: rs151012354; hg19: chr7-2565138; API