chr5-128966265-G-A

Position:

• chr5-128966265-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001017372.3(SLC27A6):​c.128G>A​(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC27A6 NM_001017372.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137

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=0.065377325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC27A6	NM_001017372.3	c.128G>A	p.Arg43Gln	missense_variant	1/10	ENST00000262462.9
SLC27A6	NM_001317984.2	c.128G>A	p.Arg43Gln	missense_variant	2/11
SLC27A6	NM_014031.5	c.128G>A	p.Arg43Gln	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A6	ENST00000262462.9	c.128G>A	p.Arg43Gln	missense_variant	1/10	1	NM_001017372.3	P1
SLC27A6	ENST00000395266.5	c.128G>A	p.Arg43Gln	missense_variant	2/11	1		P1
SLC27A6	ENST00000506176.1	c.128G>A	p.Arg43Gln	missense_variant	2/11	1		P1
SLC27A6	ENST00000508645.5	c.-62-18868G>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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

May 18, 2022

The c.128G>A (p.R43Q) 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 128, causing the arginine (R) at amino acid position 43 to be replaced by a glutamine (Q). 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	0.088
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.5
DANN	Benign	0.85
DEOGEN2	Benign	0.050	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.62	.;.;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.051	B;B;B
Vest4		0.042
MutPred		0.54		Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);
MVP		0.34
MPC		0.057
ClinPred		0.086	T
GERP RS		0.24
Varity_R		0.058
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-128301958; COSMIC: COSV52482187;