Variant 5-128985270-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.619C>T(p.Arg207Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SLC27A6
NM_001017372.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.971

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=0.032045215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A6	NM_001017372.3 linkuse as main transcript	c.619C>T	p.Arg207Cys	missense_variant	2/10	ENST00000262462.9	NP_001017372.1	Q9Y2P4
SLC27A6	NM_001317984.2 linkuse as main transcript	c.619C>T	p.Arg207Cys	missense_variant	3/11		NP_001304913.1	Q9Y2P4B2R8P6
SLC27A6	NM_014031.5 linkuse as main transcript	c.619C>T	p.Arg207Cys	missense_variant	3/11		NP_054750.1	Q9Y2P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC27A6	ENST00000262462.9 linkuse as main transcript	c.619C>T	p.Arg207Cys	missense_variant	2/10	1	NM_001017372.3	ENSP00000262462.4	Q9Y2P4
SLC27A6	ENST00000395266.5 linkuse as main transcript	c.619C>T	p.Arg207Cys	missense_variant	3/11	1		ENSP00000378684.1	Q9Y2P4
SLC27A6	ENST00000506176.1 linkuse as main transcript	c.619C>T	p.Arg207Cys	missense_variant	3/11	1		ENSP00000421024.1	Q9Y2P4
SLC27A6	ENST00000508645.5 linkuse as main transcript	c.76C>T	p.Arg26Cys	missense_variant	4/7	5		ENSP00000421759.1	D6RAJ2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251390

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1461844

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000138

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000221

Hom.:

Bravo

AF:

0.000166

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Jun 27, 2022

The c.619C>T (p.R207C) 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 619, causing the arginine (R) at amino acid position 207 to be replaced by a cysteine (C). 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

0.084

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.45

T;.;.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

.;M;M;M

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.076

Sift

Benign

0.046

D;D;D;D

Sift4G

Uncertain

0.051

T;T;T;T

Polyphen

1.0

.;D;D;D

Vest4

0.10, 0.10

MVP

0.39

MPC

0.30

ClinPred

0.12

GERP RS

3.6

Varity_R

0.080

gMVP

0.45

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.

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