5-128966473-G-A

Variant names:

• chr5-128966473-G-A
• rs1358507116
• NM_001017372.3:c.336G>A

Variant summary

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

The NM_001017372.3(SLC27A6):​c.336G>A​(p.Met112Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC27A6 NM_001017372.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A6	NM_001017372.3	c.336G>A	p.Met112Ile	missense_variant	Exon 1 of 10	ENST00000262462.9	NP_001017372.1
SLC27A6	NM_001317984.2	c.336G>A	p.Met112Ile	missense_variant	Exon 2 of 11		NP_001304913.1
SLC27A6	NM_014031.5	c.336G>A	p.Met112Ile	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.336G>A	p.Met112Ile	missense_variant	Exon 1 of 10	1	NM_001017372.3	ENSP00000262462.4
SLC27A6	ENST00000395266.5	c.336G>A	p.Met112Ile	missense_variant	Exon 2 of 11	1		ENSP00000378684.1
SLC27A6	ENST00000506176.1	c.336G>A	p.Met112Ile	missense_variant	Exon 2 of 11	1		ENSP00000421024.1
SLC27A6	ENST00000508645.5	c.-62-18660G>A		intron_variant	Intron 3 of 6	5		ENSP00000421759.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456622 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 724300

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.336G>A (p.M112I) alteration is located in exon 1 (coding exon 1) of the SLC27A6 gene. This alteration results from a G to A substitution at nucleotide position 336, causing the methionine (M) at amino acid position 112 to be replaced by an isoleucine (I). 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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.41	B;B;B
Vest4		0.59
MutPred		0.65		Loss of catalytic residue at V108 (P = 0.032);Loss of catalytic residue at V108 (P = 0.032);Loss of catalytic residue at V108 (P = 0.032);
MVP		0.51
MPC		0.30
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.35
gMVP		0.79

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: rs1358507116; hg19: chr5-128302166;