rs61743870

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001040167.2(LFNG):c.1002C>T(p.Tyr334Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,612,152 control chromosomes in the GnomAD database, including 1,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 189 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1536 hom. )

Consequence

LFNG
NM_001040167.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.59

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:

MIR4648 (HGNC:41560): (microRNA 4648) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4648 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-2526850-C-T is Benign according to our data. Variant chr7-2526850-C-T is described in ClinVar as [Benign]. Clinvar id is 257264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001040167.2 link	c.1002C>T	p.Tyr334Tyr	synonymous_variant	Exon 7 of 8	ENST00000222725.10	NP_001035257.1	Q8NES3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 link	c.1002C>T	p.Tyr334Tyr	synonymous_variant	Exon 7 of 8	5	NM_001040167.2	ENSP00000222725.5		Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6186

AN:

151710

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0484

GnomAD3 exomes

AF:

0.0516

AC:

12832

AN:

248882

Hom.:

544

AF XY:

0.0531

AC XY:

7196

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.0507

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.0211

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

AF:

0.0295

AC:

43055

AN:

1460324

Hom.:

1536

Cov.:

AF XY:

0.0319

AC XY:

23165

AN XY:

726470

show subpopulations

Gnomad4 AFR exome

AF:

0.0524

Gnomad4 AMR exome

AF:

0.0511

Gnomad4 ASJ exome

AF:

0.0284

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0527

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0392

GnomAD4 genome

AF:

0.0407

AC:

6186

AN:

151828

Hom.:

189

Cov.:

AF XY:

0.0441

AC XY:

3272

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0257

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0574

Gnomad4 NFE

AF:

0.0180

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0387

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.0192

EpiControl

AF:

0.0226

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 3, autosomal recessive

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 12, 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

-0.57

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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