Variant 7-2513172-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 11/13 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
LFNG	NM_001166355.2 linkuse as main transcript	c.63G>C	p.Trp21Cys	missense_variant	2/9		NP_001159827.1	Q8NES3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5 linkuse as main transcript	c.63G>C	p.Trp21Cys	missense_variant	2/9	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

GnomAD3 exomes

AF:

0.00422

AC:

1040

AN:

246316

Hom.:

AF XY:

0.00328

AC XY:

440

AN XY:

134064

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00340

GnomAD4 genome

AF:

0.0170

AC:

2595

AN:

152226

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1236

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0596

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0104

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.0

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

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

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over