7-2513172-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001166355.2(LFNG):c.63G>C(p.Trp21Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,613,728 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 66 hom. )

Consequence

LFNG
NM_001166355.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.610

Publications

1 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021173358).

BP6

Variant 7-2513172-G-C is Benign according to our data. Variant chr7-2513172-G-C is described in ClinVar as Benign. ClinVar VariationId is 1320690.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001166355.2 link	c.63G>C	p.Trp21Cys	missense_variant	Exon 2 of 9		NP_001159827.1	Q8NES3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5 link	c.63G>C	p.Trp21Cys	missense_variant	Exon 2 of 9	2		ENSP00000385764.1		Q8NES3-4

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2589

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0597

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00422

AC:

1040

AN:

246316

AF XY:

0.00328

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.000994

GnomAD4 exome

AF:

0.00177

AC:

2589

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1121

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.0611

AC:

2046

AN:

33470

American (AMR)

AF:

0.00342

AC:

153

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00297

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.000147

AC:

163

AN:

1111798

Other (OTH)

AF:

0.00340

AC:

205

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

128

257

385

514

642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.0170

AC:

2595

AN:

152226

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1236

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0596

AC:

2476

AN:

41516

American (AMR)

AF:

0.00510

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68018

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

126

252

379

505

631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00121

Hom.:

Bravo

AF:

0.0191

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0619

AC:

194

ESP6500EA

AF:

0.000140

AC:

ExAC

AF:

0.00530

AC:

639

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.0

(source)

DANN

Benign

0.86

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

PhyloP100

-0.61

PROVEAN

Benign

-1.1

REVEL

Benign

0.014

Sift

Pathogenic

0.0

Vest4

0.33

MutPred

0.28

Loss of helix (P = 0.0304);

MVP

0.22

ClinPred

0.040

GERP RS

0.92

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over