11-61880049-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021727.5(FADS3):c.316C>T(p.Pro106Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FADS3 NM_021727.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.17

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0381715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS3	NM_021727.5	c.316C>T	p.Pro106Ser	missense_variant	2/12	ENST00000278829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS3	ENST00000278829.7	c.316C>T	p.Pro106Ser	missense_variant	2/12	1	NM_021727.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.316C>T (p.P106S) alteration is located in exon 2 (coding exon 2) of the FADS3 gene. This alteration results from a C to T substitution at nucleotide position 316, causing the proline (P) at amino acid position 106 to be replaced by a serine (S). 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	0.082
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	4.4
Dann	Benign	0.74
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.060	N;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.24
Sift	Benign	0.63	T;T
Sift4G	Benign	0.98	T;T
Polyphen		0.0	B;.
Vest4		0.042
MutPred		0.30		Gain of phosphorylation at P106 (P = 0.1248);Gain of phosphorylation at P106 (P = 0.1248);
MVP		0.29
MPC		1.1
ClinPred		0.028	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.61

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: chr11-61647521;