9-128343153-G-T

Variant summary

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

The ENST00000372870.5(SLC27A4):c.103G>T(p.Gly35Cys) 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 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC27A4 ENST00000372870.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480

Genes affected

SLC27A4 (HGNC:10998): (solute carrier family 27 member 4) This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]

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=0.109185785).
• BP6: Variant 9-128343153-G-T is Benign according to our data. Variant chr9-128343153-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2795544.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC27A4	NM_005094.4	c.21G>T	p.Leu7=	synonymous_variant	2/13	ENST00000300456.5
SLC27A4	XM_047422664.1	c.54G>T	p.Leu18=	synonymous_variant	2/13
SLC27A4	XM_017014222.2	c.21G>T	p.Leu7=	synonymous_variant	3/14
SLC27A4	XM_024447391.2	c.21G>T	p.Leu7=	synonymous_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A4	ENST00000372870.5	c.103G>T	p.Gly35Cys	missense_variant	2/6	1
SLC27A4	ENST00000300456.5	c.21G>T	p.Leu7=	synonymous_variant	2/13	1	NM_005094.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250902 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

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: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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 Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	5.9
Dann	Benign	0.85
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.84	T
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	0.13	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Vest4		0.21
MutPred		0.47		Loss of disorder (P = 0.0219);
MVP		0.65
ClinPred		0.035	T
GERP RS		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1331404300; hg19: chr9-131105432;