7-2525485-C-T

Position:

chr7-2525485-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001040167.2(LFNG):c.653C>T(p.Pro218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,612,346 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

LFNG
NM_001040167.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.34

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:

LFNG (HGNC:):

LFNG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050231427).

BP6

Variant 7-2525485-C-T is Benign according to our data. Variant chr7-2525485-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 465828.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LFNG	NM_001040167.2 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	4/8	ENST00000222725.10	NP_001035257.1	Q8NES3-1
LFNG	NM_001040168.2 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	4/8		NP_001035258.1	Q8NES3-3
LFNG	NM_001166355.2 linkuse as main transcript	c.440C>T	p.Pro147Leu	missense_variant	5/9		NP_001159827.1	Q8NES3-4
LFNG	NM_002304.3 linkuse as main transcript	c.266C>T	p.Pro89Leu	missense_variant	5/9		NP_002295.1	Q8NES3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	4/8	5	NM_001040167.2	ENSP00000222725.5		Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000328

AC:

AN:

246696

Hom.:

AF XY:

0.000231

AC XY:

AN XY:

134358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.0000747

AC:

109

AN:

1460088

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000105

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000638

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000240

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 3, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

.;.;.;D;.;T

Eigen

Benign

-0.042

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.84

T;.;T;T;T;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.050

T;T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.5

.;.;.;M;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.6

D;D;D;D;D;.

REVEL

Benign

0.23

Sift

Uncertain

0.020

D;D;D;D;D;.

Sift4G

Uncertain

0.025

D;D;D;D;D;D

Polyphen

0.41, 0.55

.;.;.;B;P;.

Vest4

0.50

MVP

0.62

MPC

0.55

ClinPred

0.11

GERP RS

4.2

Varity_R

0.19

gMVP

0.81

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.

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