11-61876958-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_021727.5(FADS3):c.891G>C(p.Leu297Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,598,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
FADS3
NM_021727.5 missense
NM_021727.5 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 1.43
Publications
0 publications found
Genes affected
FADS3 (HGNC:3576): (fatty acid desaturase 3) The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FADS3 | NM_021727.5 | c.891G>C | p.Leu297Phe | missense_variant | Exon 8 of 12 | ENST00000278829.7 | NP_068373.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152144
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000104 AC: 15AN: 1446648Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 10AN XY: 717980 show subpopulations
GnomAD4 exome
AF:
AC:
15
AN:
1446648
Hom.:
Cov.:
31
AF XY:
AC XY:
10
AN XY:
717980
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33370
American (AMR)
AF:
AC:
0
AN:
42198
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25620
East Asian (EAS)
AF:
AC:
0
AN:
39254
South Asian (SAS)
AF:
AC:
0
AN:
83418
European-Finnish (FIN)
AF:
AC:
0
AN:
51432
Middle Eastern (MID)
AF:
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
AC:
15
AN:
1105668
Other (OTH)
AF:
AC:
0
AN:
59950
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.435
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
3
AN:
152144
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74342
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41426
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68026
Other (OTH)
AF:
AC:
0
AN:
2090
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000034), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.392
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jul 02, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.891G>C (p.L297F) alteration is located in exon 8 (coding exon 8) of the FADS3 gene. This alteration results from a G to C substitution at nucleotide position 891, causing the leucine (L) at amino acid position 297 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;L;.;.;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;D;D
Sift4G
Benign
T;T;T;.;.
Polyphen
P;B;.;.;.
Vest4
MutPred
0.69
.;Loss of catalytic residue at L297 (P = 0.1858);.;.;.;
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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