dbSNP rs199975806: FADS6:p.Arg275Leu (chr17-74879540-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178128.6(FADS6):c.824G>T(p.Arg275Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,613,446 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R275Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 1 hom. )

Consequence

FADS6
NM_178128.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03998846).

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.824G>T	p.Arg275Leu	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.824G>T	p.Arg275Leu	missense	Exon 5 of 6	ENSP00000481684.1	A0A087WYB9
FADS6	ENST00000958198.1		c.950G>T	p.Arg317Leu	missense	Exon 5 of 6	ENSP00000628257.1
FADS6	ENST00000579663.1	TSL:3	c.407G>T	p.Arg136Leu	missense	Exon 3 of 3	ENSP00000464267.1	J3QRK6

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000169

AC:

AN:

248450

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.00272

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1461182

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

726858

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

33464

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5514

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111808

Other (OTH)

AF:

0.0000995

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000670

AC:

102

AN:

152264

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00243

AC:

101

AN:

41538

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000393

Hom.:

Bravo

AF:

0.000703

ESP6500AA

AF:

0.00291

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000174

AC:

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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.1

PhyloP100

5.6

PrimateAI

Uncertain

0.55

Sift4G

Pathogenic

0.0

Vest4

0.86

MVP

0.34

ClinPred

0.19

GERP RS

5.5

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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