Variant 5-128966361-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000262462.9(SLC27A6):c.224A>G(p.Tyr75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC27A6
ENST00000262462.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

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]

SLC27A6 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein
SLC27A6	NM_001017372.3 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	1/10	ENST00000262462.9	NP_001017372.1
SLC27A6	NM_001317984.2 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	2/11		NP_001304913.1
SLC27A6	NM_014031.5 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	2/11		NP_054750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SLC27A6	ENST00000262462.9 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	1/10	1	NM_001017372.3	ENSP00000262462	P1
SLC27A6	ENST00000395266.5 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	2/11	1		ENSP00000378684	P1
SLC27A6	ENST00000506176.1 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	2/11	1		ENSP00000421024	P1
SLC27A6	ENST00000508645.5 linkuse as main transcript	c.-62-18772A>G		intron_variant		5		ENSP00000421759

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727160

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.224A>G (p.Y75C) 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 224, causing the tyrosine (Y) at amino acid position 75 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

0.083

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

.;.;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.018

D;D;D

Sift4G

Benign

0.068

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.67

MutPred

0.62

Loss of catalytic residue at I74 (P = 0.0512);Loss of catalytic residue at I74 (P = 0.0512);Loss of catalytic residue at I74 (P = 0.0512);

MVP

0.64

MPC

0.34

ClinPred

0.96

GERP RS

4.2

Varity_R

0.49

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over