GeneBe

2-58161561-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_018062.4(FANCL):​c.981T>A​(p.Ser327Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S327S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FANCL
NM_018062.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.551

Publications

38 publications found
Variant links:
Genes affected
FANCL (HGNC:20748): (FA complementation group L) This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]
FANCL Gene-Disease associations (from GenCC):
  • Fanconi anemia complementation group L
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Laboratory for Molecular Medicine
  • Fanconi anemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP7
Synonymous conserved (PhyloP=-0.551 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FANCLNM_018062.4 linkc.981T>A p.Ser327Ser synonymous_variant Exon 12 of 14 ENST00000233741.9 NP_060532.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FANCLENST00000233741.9 linkc.981T>A p.Ser327Ser synonymous_variant Exon 12 of 14 1 NM_018062.4 ENSP00000233741.5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1458962
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
725936
African (AFR)
AF:
0.00
AC:
0
AN:
33386
American (AMR)
AF:
0.00
AC:
0
AN:
44660
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26062
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39570
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53398
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1109658
Other (OTH)
AF:
0.00
AC:
0
AN:
60284
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
139602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
1.3
DANN
Benign
0.83
PhyloP100
-0.55
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs848291; hg19: chr2-58388696; API