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GeneBe

6-53269224-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021814.5(ELOVL5):c.803A>G(p.Asp268Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.000014 ( 0 hom. )

Consequence

ELOVL5
NM_021814.5 missense

Scores

1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18
Variant links:
Genes affected
ELOVL5 (HGNC:21308): (ELOVL fatty acid elongase 5) This gene belongs to the ELO family. It is highly expressed in the adrenal gland and testis, and encodes a multi-pass membrane protein that is localized in the endoplasmic reticulum. This protein is involved in the elongation of long-chain polyunsaturated fatty acids. Mutations in this gene have been associated with spinocerebellar ataxia-38 (SCA38). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07160646).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ELOVL5NM_021814.5 linkuse as main transcriptc.803A>G p.Asp268Gly missense_variant 8/8 ENST00000304434.11
ELOVL5NM_001242828.2 linkuse as main transcriptc.884A>G p.Asp295Gly missense_variant 9/9
ELOVL5NM_001301856.2 linkuse as main transcriptc.803A>G p.Asp268Gly missense_variant 8/8
ELOVL5NM_001242830.2 linkuse as main transcriptc.678A>G p.Gly226= synonymous_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ELOVL5ENST00000304434.11 linkuse as main transcriptc.803A>G p.Asp268Gly missense_variant 8/81 NM_021814.5 P1Q9NYP7-1
ELOVL5ENST00000542638.5 linkuse as main transcriptc.678A>G p.Gly226= synonymous_variant 7/71
ELOVL5ENST00000370918.8 linkuse as main transcriptc.884A>G p.Asp295Gly missense_variant 9/92 Q9NYP7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249470
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134918
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:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461120
Hom.:
0
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
726832
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:
0.000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeApr 07, 2022This variant is present in population databases (rs775550239, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 268 of the ELOVL5 protein (p.Asp268Gly). This variant has not been reported in the literature in individuals affected with ELOVL5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.56
Cadd
Benign
20
Dann
Benign
0.96
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.97
D;D;D;D
PrimateAI
Benign
0.35
T
REVEL
Benign
0.029
Sift4G
Benign
0.38
T;T
Polyphen
0.0
.;B
Vest4
0.14
MutPred
0.24
.;Gain of sheet (P = 0.0266);
MVP
0.13
ClinPred
0.027
T
GERP RS
3.2
Varity_R
0.045
gMVP
0.42

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.

Other links and lift over

dbSNP: rs775550239; hg19: chr6-53134022; API