Variant 5-128985309-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001017372.3(SLC27A6):c.658C>T(p.Leu220Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SLC27A6
NM_001017372.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

Variant links:

Genes affected

SLC27A6 (HGNC:11000): (solute carrier family 27 member 6) This gene encodes a member of the fatty acid transport protein family (FATP). FATPs are involved in the uptake of long-chain fatty acids and have unique expression patterns. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

SLC27A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038590103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC27A6	NM_001017372.3 linkuse as main transcript	c.658C>T	p.Leu220Phe	missense_variant	2/10	ENST00000262462.9
SLC27A6	NM_001317984.2 linkuse as main transcript	c.658C>T	p.Leu220Phe	missense_variant	3/11
SLC27A6	NM_014031.5 linkuse as main transcript	c.658C>T	p.Leu220Phe	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC27A6	ENST00000262462.9 linkuse as main transcript	c.658C>T	p.Leu220Phe	missense_variant	2/10	1	NM_001017372.3	P1
SLC27A6	ENST00000395266.5 linkuse as main transcript	c.658C>T	p.Leu220Phe	missense_variant	3/11	1		P1
SLC27A6	ENST00000506176.1 linkuse as main transcript	c.658C>T	p.Leu220Phe	missense_variant	3/11	1		P1
SLC27A6	ENST00000508645.5 linkuse as main transcript	c.115C>T	p.Leu39Phe	missense_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251274

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000267

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000486

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000821

Hom.:

Bravo

AF:

0.000491

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.658C>T (p.L220F) alteration is located in exon 2 (coding exon 2) of the SLC27A6 gene. This alteration results from a C to T substitution at nucleotide position 658, causing the leucine (L) at amino acid position 220 to be replaced by a phenylalanine (F). 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

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.061

T;T;T;T

Eigen

Benign

0.0059

Eigen_PC

Benign

-0.097

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.92

D;.;.;D

M_CAP

Benign

0.0072

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.026

D;D;D;D

Sift4G

Benign

0.11

T;D;D;D

Polyphen

0.87

.;P;P;P

Vest4

0.48, 0.48, 0.48

MVP

0.32

MPC

0.34

ClinPred

0.20

GERP RS

3.6

Varity_R

0.23

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over