dbSNP rs1844102537: ACSL5:p.Ile174Val (chr10-112408509-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_203379.2(ACSL5):c.520A>G(p.Ile174Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)

Consequence

ACSL5
NM_203379.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

Publications

0 publications found

Variant links:

Genes affected

ACSL5 (HGNC:16526): (acyl-CoA synthetase long chain family member 5) The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme is highly expressed in uterus and spleen, and in trace amounts in normal brain, but has markedly increased levels in malignant gliomas. This gene functions in mediating fatty acid-induced glioma cell growth. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACSL5 Gene-Disease associations (from GenCC):

diarrhea 13
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACSL5 links:

ENSG00000232934 (HGNC:):

ENSG00000232934 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31371367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203379.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSL5	NM_203379.2	MANE Select	c.520A>G	p.Ile174Val	missense	Exon 6 of 21	NP_976313.1	Q9ULC5-1
ACSL5	NM_016234.4		c.688A>G	p.Ile230Val	missense	Exon 6 of 21	NP_057318.2
ACSL5	NM_001387037.1		c.688A>G	p.Ile230Val	missense	Exon 6 of 20	NP_001373966.1	A0A8C8L3F5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSL5	ENST00000354655.9	TSL:2 MANE Select	c.520A>G	p.Ile174Val	missense	Exon 6 of 21	ENSP00000346680.4	Q9ULC5-1
ACSL5	ENST00000356116.6	TSL:1	c.688A>G	p.Ile230Val	missense	Exon 6 of 21	ENSP00000348429.1	Q9ULC5-3
ACSL5	ENST00000354273.5	TSL:1	c.688A>G	p.Ile230Val	missense	Exon 6 of 19	ENSP00000346223.5	A0A8C8KCK5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Benign

0.14

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

M_CAP

Benign

0.049

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

PhyloP100

7.5

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.86

REVEL

Benign

0.17

Sift

Benign

0.041

Sift4G

Uncertain

0.051

Polyphen

0.56

Vest4

0.28

MutPred

0.60

Loss of ubiquitination at K177 (P = 0.1079)

MVP

0.44

MPC

0.16

ClinPred

0.69

GERP RS

4.8

Varity_R

0.15

gMVP

0.37

Mutation Taster

=58/42

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over