11-61891359-C-T

Position:

chr11-61891359-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021727.5(FADS3):c.23G>A(p.Gly8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000539 in 1,485,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

FADS3
NM_021727.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.424

Variant links:

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]

FADS3 links:

FADS3 (HGNC:):

FADS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10285139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS3	NM_021727.5 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	1/12	ENST00000278829.7	NP_068373.1	Q9Y5Q0A0A024R564
FADS3	XM_011545023.2 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	1/12		XP_011543325.1
FADS3	XM_017017723.1 linkuse as main transcript	c.351+500G>A		intron_variant			XP_016873212.1
FADS3	XM_017017724.1 linkuse as main transcript	c.351+500G>A		intron_variant			XP_016873213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS3	ENST00000278829.7 linkuse as main transcript	c.23G>A	p.Gly8Glu	missense_variant	1/12	1	NM_021727.5	ENSP00000278829.2		Q9Y5Q0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000435

AC:

AN:

92048

Hom.:

AF XY:

0.0000779

AC XY:

AN XY:

51370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000222

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000525

AC:

AN:

1333064

Hom.:

Cov.:

AF XY:

0.00000918

AC XY:

AN XY:

653538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 07, 2024

The c.23G>A (p.G8E) alteration is located in exon 1 (coding exon 1) of the FADS3 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the glycine (G) at amino acid position 8 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.046

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.94

L;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.11

Sift

Benign

0.24

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.82

P;.

Vest4

0.21

MutPred

0.24

Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);

MVP

0.28

MPC

1.4

ClinPred

0.20

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.78

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