11-61876951-C-T

Variant names:

• chr11-61876951-C-T
• NM_021727.5:c.898G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021727.5(FADS3):​c.898G>A​(p.Ala300Thr) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A300V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FADS3 NM_021727.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.914

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31602415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS3	NM_021727.5	c.898G>A	p.Ala300Thr	missense_variant	Exon 8 of 12	ENST00000278829.7	NP_068373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS3	ENST00000278829.7	c.898G>A	p.Ala300Thr	missense_variant	Exon 8 of 12	1	NM_021727.5	ENSP00000278829.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450064 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.898G>A (p.A300T) alteration is located in exon 8 (coding exon 8) of the FADS3 gene. This alteration results from a G to A substitution at nucleotide position 898, causing the alanine (A) at amino acid position 300 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T;T;T;.;.
Eigen	Benign	-0.074
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	.;L;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.27	T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;.;.
Polyphen		0.0050	B;B;.;.;.
Vest4		0.43
MutPred		0.63		.;Gain of catalytic residue at F303 (P = 0.1146);.;.;.;
MVP		0.66
MPC		1.1
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-61644423;