17-74881126-C-T

Variant summary

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

The NM_178128.6(FADS6):​c.722G>A​(p.Cys241Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,508 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

FADS6
NM_178128.6 missense

Scores

2
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43
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=0.40283597).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FADS6NM_178128.6 linkc.722G>A p.Cys241Tyr missense_variant Exon 4 of 6 ENST00000612771.5 NP_835229.3 Q8N9I5A0A087WYB9
FADS6XM_005257224.6 linkc.722G>A p.Cys241Tyr missense_variant Exon 4 of 7 XP_005257281.2
FADS6XM_017024458.3 linkc.668G>A p.Cys223Tyr missense_variant Exon 5 of 8 XP_016879947.1
FADS6XM_047435759.1 linkc.263G>A p.Cys88Tyr 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.722G>A p.Cys241Tyr missense_variant Exon 4 of 6 1 NM_178128.6 ENSP00000481684.1 A0A087WYB9
FADS6ENST00000579663.1 linkc.305G>A p.Cys102Tyr missense_variant Exon 2 of 3 3 ENSP00000464267.1 J3QRK6
FADS6ENST00000413142.2 linkn.355+1404G>A intron_variant Intron 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152206
Hom.:
1
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:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000109
AC:
27
AN:
247488
Hom.:
0
AF XY:
0.000163
AC XY:
22
AN XY:
134584
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000887
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000520
AC:
76
AN:
1461302
Hom.:
0
Cov.:
31
AF XY:
0.0000757
AC XY:
55
AN XY:
726872
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:
0.000859
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152206
Hom.:
1
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74360
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:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.000141
AC:
17
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.668G>A (p.C223Y) 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 668, causing the cysteine (C) at amino acid position 223 to be replaced by a tyrosine (Y). 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
-0.067
T
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.79
T
Sift4G
Pathogenic
0.0010
D;D;D
Vest4
0.94
MVP
0.37
ClinPred
0.71
D
GERP RS
5.1

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: rs552387918; hg19: chr17-72877256; API