5-128966546-A-G

Variant names:

• chr5-128966546-A-G
• NM_001017372.3:c.409A>G

Variant summary

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

The NM_001017372.3(SLC27A6):​c.409A>G​(p.Thr137Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000042 in 1,429,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. T137S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: SLC27A6 NM_001017372.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.196

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=0.18177709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A6	NM_001017372.3	c.409A>G	p.Thr137Ala	missense_variant	Exon 1 of 10	ENST00000262462.9	NP_001017372.1
SLC27A6	NM_001317984.2	c.409A>G	p.Thr137Ala	missense_variant	Exon 2 of 11		NP_001304913.1
SLC27A6	NM_014031.5	c.409A>G	p.Thr137Ala	missense_variant	Exon 2 of 11		NP_054750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC27A6	ENST00000262462.9	c.409A>G	p.Thr137Ala	missense_variant	Exon 1 of 10	1	NM_001017372.3	ENSP00000262462.4
SLC27A6	ENST00000395266.5	c.409A>G	p.Thr137Ala	missense_variant	Exon 2 of 11	1		ENSP00000378684.1
SLC27A6	ENST00000506176.1	c.409A>G	p.Thr137Ala	missense_variant	Exon 2 of 11	1		ENSP00000421024.1
SLC27A6	ENST00000508645.5	c.-62-18587A>G		intron_variant	Intron 3 of 6	5		ENSP00000421759.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000420 AC: 6 AN: 1429982 Hom.: 0 Cov.: 34 AF XY: 0.00000423 AC XY: 3 AN XY: 709200

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: 0.0000501

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.409A>G (p.T137A) alteration is located in exon 1 (coding exon 1) of the SLC27A6 gene. This alteration results from a A to G substitution at nucleotide position 409, causing the threonine (T) at amino acid position 137 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.76
DEOGEN2	Benign	0.051	T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.53	.;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.9	M;M;M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.044
MutPred		0.61		Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);
MVP		0.41
MPC		0.051
ClinPred		0.62	D
GERP RS		1.7
Varity_R		0.046
gMVP		0.23

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: chr5-128302239;