17-74881219-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178128.6(FADS6):​c.629G>A​(p.Arg210Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,607,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 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. R210W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FADS6
NM_178128.6 missense

Scores

3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69
Variant links:
Genes affected
FADS6 (HGNC:30459): (fatty acid desaturase 6) Predicted to enable oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water. Predicted to be involved in lipid metabolic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.28530827).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FADS6NM_178128.6 linkc.629G>A p.Arg210Gln missense_variant Exon 4 of 6 ENST00000612771.5 NP_835229.3 Q8N9I5A0A087WYB9
FADS6XM_005257224.6 linkc.629G>A p.Arg210Gln missense_variant Exon 4 of 7 XP_005257281.2
FADS6XM_017024458.3 linkc.575G>A p.Arg192Gln missense_variant Exon 5 of 8 XP_016879947.1
FADS6XM_047435759.1 linkc.170G>A p.Arg57Gln missense_variant Exon 3 of 6 XP_047291715.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FADS6ENST00000612771.5 linkc.629G>A p.Arg210Gln missense_variant Exon 4 of 6 1 NM_178128.6 ENSP00000481684.1 A0A087WYB9
FADS6ENST00000579663.1 linkc.212G>A p.Arg71Gln missense_variant Exon 2 of 3 3 ENSP00000464267.1 J3QRK6
FADS6ENST00000413142.2 linkn.355+1311G>A intron_variant Intron 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1455384
Hom.:
0
Cov.:
31
AF XY:
0.00000415
AC XY:
3
AN XY:
723480
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.575G>A (p.R192Q) alteration is located in exon 4 (coding exon 4) of the FADS6 gene. This alteration results from a G to A substitution at nucleotide position 575, causing the arginine (R) at amino acid position 192 to be replaced by a glutamine (Q). 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
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
1.0
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.22
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.73
T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.39
T
Sift4G
Uncertain
0.027
D;D;D
Vest4
0.15
MVP
0.28
ClinPred
0.91
D
GERP RS
4.1

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.

Other links and lift over

dbSNP: rs1325584142; hg19: chr17-72877349; API