5-128985270-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.971

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]

ACMG classification

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	UniProt
SLC27A6	NM_001017372.3	c.619C>T	p.Arg207Cys	missense_variant	2/10	ENST00000262462.9
SLC27A6	NM_001317984.2	c.619C>T	p.Arg207Cys	missense_variant	3/11
SLC27A6	NM_014031.5	c.619C>T	p.Arg207Cys	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A6	ENST00000262462.9	c.619C>T	p.Arg207Cys	missense_variant	2/10	1	NM_001017372.3	P1
SLC27A6	ENST00000395266.5	c.619C>T	p.Arg207Cys	missense_variant	3/11	1		P1
SLC27A6	ENST00000506176.1	c.619C>T	p.Arg207Cys	missense_variant	3/11	1		P1
SLC27A6	ENST00000508645.5	c.76C>T	p.Arg26Cys	missense_variant	4/7	5

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152158 Hom.: 0 Cov.: 33

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: 38 AN: 251390 Hom.: 0 AF XY: 0.000184 AC XY: 25 AN XY: 135880

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.: 0 Cov.: 31 AF XY: 0.000132 AC XY: 96 AN XY: 727224

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: 21 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74326

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.: 0

Bravo AF: 0.000166

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	17
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	N
LIST_S2	Benign	0.45	T;.;.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.032	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.20	T
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	T
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

Other links and lift over

dbSNP: rs201991962; hg19: chr5-128320963; COSMIC: COSV99323562;