Genetic Variant FADS6:p.Arg274Cys (chr17-74879544-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178128.6(FADS6):c.820C>T(p.Arg274Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,613,208 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 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. R274H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000085 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000081 ( 1 hom. )

Consequence

FADS6
NM_178128.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

Publications

2 publications found

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]

FADS6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08548832).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178128.6. 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
	FADS6	NM_178128.6	MANE Select	c.820C>T	p.Arg274Cys	missense	Exon 5 of 6	NP_835229.3	A0A087WYB9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FADS6	ENST00000612771.5	TSL:1 MANE Select	c.820C>T	p.Arg274Cys	missense	Exon 5 of 6	ENSP00000481684.1	A0A087WYB9
FADS6	ENST00000958198.1		c.946C>T	p.Arg316Cys	missense	Exon 5 of 6	ENSP00000628257.1
FADS6	ENST00000579663.1	TSL:3	c.403C>T	p.Arg135Cys	missense	Exon 3 of 3	ENSP00000464267.1	J3QRK6

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000145

AC:

AN:

248288

AF XY:

0.000185

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000808

AC:

118

AN:

1461024

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

726770

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33456

American (AMR)

AF:

0.0000895

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000696

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.0000563

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5400

European-Non Finnish (NFE)

AF:

0.0000414

AC:

AN:

1111808

Other (OTH)

AF:

0.0000332

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000182

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.086

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.027

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.1

PhyloP100

2.3

PrimateAI

Benign

0.28

Sift4G

Pathogenic

0.0010

Vest4

0.43

MVP

0.26

ClinPred

0.42

GERP RS

3.4

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over