9-128348613-G-T

Variant names:

• chr9-128348613-G-T
• NM_005094.4:c.625G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005094.4(SLC27A4):​c.625G>T​(p.Gly209Cys) 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 1,461,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G209S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC27A4 NM_005094.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087828904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A4	NM_005094.4	c.625G>T	p.Gly209Cys	missense_variant	Exon 4 of 13	ENST00000300456.5	NP_005085.2
SLC27A4	XM_047422664.1	c.658G>T	p.Gly220Cys	missense_variant	Exon 4 of 13		XP_047278620.1
SLC27A4	XM_017014222.2	c.625G>T	p.Gly209Cys	missense_variant	Exon 5 of 14		XP_016869711.1
SLC27A4	XM_024447391.2	c.625G>T	p.Gly209Cys	missense_variant	Exon 5 of 14		XP_024303159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC27A4	ENST00000300456.5	c.625G>T	p.Gly209Cys	missense_variant	Exon 4 of 13	1	NM_005094.4	ENSP00000300456.3
SLC27A4	ENST00000372870.5	c.231+5332G>T		intron_variant	Intron 2 of 5	1		ENSP00000361961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461494 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727058

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.027
Sift	Benign	0.037	D
Sift4G	Uncertain	0.050	T
Polyphen		0.066	B
Vest4		0.14
MutPred		0.43		Gain of catalytic residue at P208 (P = 0.0135);
MVP		0.49
MPC		0.30
ClinPred		0.17	T
GERP RS		0.64
Varity_R		0.10
gMVP		0.35

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.

Other links and lift over

hg19: chr9-131110892; COSMIC: COSV55961228;