5-128966547-C-G

Variant names:

• chr5-128966547-C-G
• rs1195060105
• NM_001017372.3:c.410C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001017372.3(SLC27A6):​c.410C>G​(p.Thr137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,581,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T137A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC27A6 NM_001017372.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.165

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=0.14034614).
• BP6: Variant 5-128966547-C-G is Benign according to our data. Variant chr5-128966547-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3319392.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A6	NM_001017372.3	c.410C>G	p.Thr137Ser	missense_variant	Exon 1 of 10	ENST00000262462.9	NP_001017372.1
SLC27A6	NM_001317984.2	c.410C>G	p.Thr137Ser	missense_variant	Exon 2 of 11		NP_001304913.1
SLC27A6	NM_014031.5	c.410C>G	p.Thr137Ser	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.410C>G	p.Thr137Ser	missense_variant	Exon 1 of 10	1	NM_001017372.3	ENSP00000262462.4
SLC27A6	ENST00000395266.5	c.410C>G	p.Thr137Ser	missense_variant	Exon 2 of 11	1		ENSP00000378684.1
SLC27A6	ENST00000506176.1	c.410C>G	p.Thr137Ser	missense_variant	Exon 2 of 11	1		ENSP00000421024.1
SLC27A6	ENST00000508645.5	c.-62-18586C>G		intron_variant	Intron 3 of 6	5		ENSP00000421759.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000928 AC: 2 AN: 215456 Hom.: 0 AF XY: 0.00000869 AC XY: 1 AN XY: 115134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000669

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429358 Hom.: 0 Cov.: 34 AF XY: 0.00000141 AC XY: 1 AN XY: 708800

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000498

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: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 02, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.046	T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.18	.;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.47	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.036
MutPred		0.55		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.52
MPC		0.047
ClinPred		0.13	T
GERP RS		4.2
Varity_R		0.038
gMVP		0.19

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: rs1195060105; hg19: chr5-128302240;