NM_013402.7:c.116C>A

Variant names:

• chr11-61816814-G-T
• rs555414942
• NM_013402.7:c.116C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013402.7(FADS1):​c.116C>A​(p.Pro39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000522 in 1,340,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P39R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: FADS1 NM_013402.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 0 publications found

Genes affected

FADS1 (HGNC:3574): (fatty acid desaturase 1) 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]

FADS2 (HGNC:3575): (fatty acid desaturase 2) 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 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117648125).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013402.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	NM_013402.7	MANE Select	c.116C>A	p.Pro39Gln	missense	Exon 1 of 12	NP_037534.5
	FADS2	NM_001281501.1		c.141+388G>T		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.114+118G>T		intron	N/A	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.116C>A	p.Pro39Gln	missense	Exon 1 of 12	ENSP00000322229.9	A0A0A0MR51
	FADS2	ENST00000257261.10	TSL:1	c.141+388G>T		intron	N/A	ENSP00000257261.6	O95864-2
	FADS1	ENST00000935427.1		c.116C>A	p.Pro39Gln	missense	Exon 1 of 12	ENSP00000605486.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000522 AC: 7 AN: 1340828 Hom.: 0 Cov.: 31 AF XY: 0.00000454 AC XY: 3 AN XY: 661138

African (AFR) AF: 0.00 AC: 0 AN: 26920

American (AMR) AF: 0.00 AC: 0 AN: 26274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22802

East Asian (EAS) AF: 0.00 AC: 0 AN: 32556

South Asian (SAS) AF: 0.00 AC: 0 AN: 73170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4010

European-Non Finnish (NFE) AF: 0.00000658 AC: 7 AN: 1063932

Other (OTH) AF: 0.00 AC: 0 AN: 55748

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.3
DANN	Benign	0.87
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.42
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.026
Sift	Benign	0.088	T
Sift4G	Benign	0.35	T
Vest4		0.10
MutPred		0.23		Loss of glycosylation at P39 (P = 0.0125)
MVP		0.16
MPC		2.4
ClinPred		0.092	T
GERP RS		-3.3
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
gMVP		0.13
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs555414942; hg19: chr11-61584286;