rs12700028

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001040167.2(LFNG):c.972G>A(p.Ser324Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 1,608,466 control chromosomes in the GnomAD database, including 2,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 170 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2755 hom. )

Consequence

LFNG
NM_001040167.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -8.23

Publications

12 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, Labcorp Genetics (formerly Invitae), G2P
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LFNG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-2526394-G-A is Benign according to our data. Variant chr7-2526394-G-A is described in ClinVar as Benign. ClinVar VariationId is 257271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LFNG	NM_001040167.2 link	c.972G>A	p.Ser324Ser	synonymous_variant	Exon 6 of 8	ENST00000222725.10	NP_001035257.1
LFNG	NM_001040168.2 link	c.972G>A	p.Ser324Ser	synonymous_variant	Exon 6 of 8		NP_001035258.1
LFNG	NM_001166355.2 link	c.759G>A	p.Ser253Ser	synonymous_variant	Exon 7 of 9		NP_001159827.1
LFNG	NM_002304.3 link	c.585G>A	p.Ser195Ser	synonymous_variant	Exon 7 of 9		NP_002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 link	c.972G>A	p.Ser324Ser	synonymous_variant	Exon 6 of 8	5	NM_001040167.2	ENSP00000222725.5

Frequencies

GnomAD3 genomes

AF:

0.0405

AC:

6163

AN:

152034

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0434

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0622

Gnomad OTH

AF:

0.0388

GnomAD2 exomes

AF:

0.0425

AC:

10446

AN:

245624

AF XY:

0.0424

show subpopulations

Gnomad AFR exome

AF:

0.00927

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0389

Gnomad EAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.0484

Gnomad NFE exome

AF:

0.0590

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0570

AC:

82998

AN:

1456316

Hom.:

2755

Cov.:

AF XY:

0.0559

AC XY:

40519

AN XY:

724686

show subpopulations

African (AFR)

AF:

0.00860

AC:

288

AN:

33474

American (AMR)

AF:

0.0451

AC:

2016

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

1017

AN:

26124

East Asian (EAS)

AF:

0.000630

AC:

AN:

39696

South Asian (SAS)

AF:

0.0203

AC:

1749

AN:

86254

European-Finnish (FIN)

AF:

0.0493

AC:

2369

AN:

48044

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0652

AC:

72531

AN:

1111890

Other (OTH)

AF:

0.0485

AC:

2929

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4348

8696

13045

17393

21741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2680

5360

8040

10720

13400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0405

AC:

6161

AN:

152150

Hom.:

170

Cov.:

AF XY:

0.0388

AC XY:

2885

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0114

AC:

475

AN:

41534

American (AMR)

AF:

0.0433

AC:

662

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

155

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5174

South Asian (SAS)

AF:

0.0164

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0434

AC:

460

AN:

10606

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0622

AC:

4227

AN:

67946

Other (OTH)

AF:

0.0384

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

292

584

875

1167

1459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0521

Hom.:

139

Bravo

AF:

0.0389

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0574

EpiControl

AF:

0.0565

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Spondylocostal dysostosis 3, autosomal recessive

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Sep 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.43

(source)

DANN

Benign

0.67

PhyloP100

-8.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over