Variant chr19-17486574-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198580.3(SLC27A1):c.179T>C(p.Val60Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000441 in 1,587,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

SLC27A1
NM_198580.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A1	NM_198580.3 linkuse as main transcript	c.179T>C	p.Val60Ala	missense_variant	2/12	ENST00000252595.12	NP_940982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A1	ENST00000252595.12 linkuse as main transcript	c.179T>C	p.Val60Ala	missense_variant	2/12	1	NM_198580.3	ENSP00000252595	P1	Q6PCB7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000488

AC:

AN:

204964

Hom.:

AF XY:

0.00000878

AC XY:

AN XY:

113882

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:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000418

AC:

AN:

1435322

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713684

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:

0.00000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000842

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

Mar 24, 2023

The c.179T>C (p.V60A) alteration is located in exon 2 (coding exon 2) of the SLC27A1 gene. This alteration results from a T to C substitution at nucleotide position 179, causing the valine (V) at amino acid position 60 to be replaced by an alanine (A). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.14

Eigen

Benign

0.021

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.76

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.78

REVEL

Benign

0.20

Sift

Benign

0.73

Sift4G

Benign

0.62

Polyphen

0.58

Vest4

0.87

MutPred

0.43

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.77

MPC

0.46

ClinPred

0.36

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.81

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

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