Variant 19-17497351-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_198580.3(SLC27A1):c.1093G>C(p.Gly365Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,601,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC27A1
NM_198580.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.36

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:

PGLS-DT (HGNC:55274): (PGLS divergent transcript)

PGLS-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A1	NM_198580.3 linkuse as main transcript	c.1093G>C	p.Gly365Arg	missense_variant	7/12	ENST00000252595.12	NP_940982.1
PGLS-DT	NR_147835.1 linkuse as main transcript	n.548-6154C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A1	ENST00000252595.12 linkuse as main transcript	c.1093G>C	p.Gly365Arg	missense_variant	7/12	1	NM_198580.3	ENSP00000252595	P1	Q6PCB7-1
PGLS-DT	ENST00000596643.5 linkuse as main transcript	n.548-6154C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

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

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1449432

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721562

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

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:

0.0000151

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

Nov 15, 2021

The c.1093G>C (p.G365R) alteration is located in exon 7 (coding exon 7) of the SLC27A1 gene. This alteration results from a G to C substitution at nucleotide position 1093, causing the glycine (G) at amino acid position 365 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Pathogenic

4.3

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.7

D;.

REVEL

Uncertain

0.60

Sift

Uncertain

0.018

D;.

Sift4G

Uncertain

0.020

D;D

Polyphen

0.98

D;.

Vest4

0.96

MutPred

0.86

Gain of MoRF binding (P = 0.0243);.;

MVP

0.82

MPC

1.2

ClinPred

1.0

GERP RS

4.4

Varity_R

0.62

gMVP

0.93

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