5-128988645-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017372.3(SLC27A6):c.731G>T(p.Gly244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC27A6 NM_001017372.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.907

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15671736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC27A6	NM_001017372.3	c.731G>T	p.Gly244Val	missense_variant	3/10	ENST00000262462.9
SLC27A6	NM_001317984.2	c.731G>T	p.Gly244Val	missense_variant	4/11
SLC27A6	NM_014031.5	c.731G>T	p.Gly244Val	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A6	ENST00000262462.9	c.731G>T	p.Gly244Val	missense_variant	3/10	1	NM_001017372.3	P1
SLC27A6	ENST00000395266.5	c.731G>T	p.Gly244Val	missense_variant	4/11	1		P1
SLC27A6	ENST00000506176.1	c.731G>T	p.Gly244Val	missense_variant	4/11	1		P1
SLC27A6	ENST00000508645.5	c.188G>T	p.Gly63Val	missense_variant	5/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461784 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000331

GnomAD4 genome Cov.: 32

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

Oct 06, 2021

The c.731G>T (p.G244V) alteration is located in exon 3 (coding exon 3) of the SLC27A6 gene. This alteration results from a G to T substitution at nucleotide position 731, causing the glycine (G) at amino acid position 244 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	15
Dann	Benign	0.83
DEOGEN2	Benign	0.0090	T;T;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T;.;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.061
Sift	Benign	0.70	T;T;T;T
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.028	.;B;B;B
Vest4		0.55
MutPred		0.69		.;Loss of methylation at R243 (P = 0.0602);Loss of methylation at R243 (P = 0.0602);Loss of methylation at R243 (P = 0.0602);
MVP		0.37
MPC		0.11
ClinPred		0.16	T
GERP RS		0.14
Varity_R		0.10
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-128324338;