Variant chr19-17486775-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198580.3(SLC27A1):c.380C>G(p.Pro127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,452,526 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC27A1
NM_198580.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

SLC27A1 (HGNC:10995): (solute carrier family 27 member 1) Enables biotin transmembrane transporter activity; efflux transmembrane transporter activity; and long-chain fatty acid transporter activity. Involved in several processes, including carboxylic acid transmembrane transport; glycerophospholipid biosynthetic process; and lipid transport across blood-brain barrier. Located in membrane. Part of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC27A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.20932516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A1	NM_198580.3 linkuse as main transcript	c.380C>G	p.Pro127Arg	missense_variant	2/12	ENST00000252595.12	NP_940982.1	Q6PCB7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A1	ENST00000252595.12 linkuse as main transcript	c.380C>G	p.Pro127Arg	missense_variant	2/12	1	NM_198580.3	ENSP00000252595.6		Q6PCB7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

232710

Hom.:

AF XY:

0.0000236

AC XY:

AN XY:

126934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000290

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1452526

Hom.:

Cov.:

AF XY:

0.00000970

AC XY:

AN XY:

721728

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

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

Apr 20, 2024

The c.380C>G (p.P127R) alteration is located in exon 2 (coding exon 2) of the SLC27A1 gene. This alteration results from a C to G substitution at nucleotide position 380, causing the proline (P) at amino acid position 127 to be replaced by an arginine (R). 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

0.074

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.075

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.68

M_CAP

Benign

0.036

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.66

REVEL

Benign

0.069

Sift

Benign

0.43

Sift4G

Benign

0.48

Polyphen

0.12

Vest4

0.28

MutPred

0.49

Gain of methylation at P127 (P = 0.0186);

MVP

0.59

MPC

0.41

ClinPred

0.11

GERP RS

3.9

Varity_R

0.041

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over