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GeneBe

6-53269156-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_021814.5(ELOVL5):c.871G>A(p.Val291Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,613,918 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ELOVL5
NM_021814.5 missense

Scores

3
9

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.46
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.080304325).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-53269156-C-T is Benign according to our data. Variant chr6-53269156-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2070080.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 50 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ELOVL5NM_021814.5 linkuse as main transcriptc.871G>A p.Val291Met missense_variant 8/8 ENST00000304434.11
ELOVL5NM_001242828.2 linkuse as main transcriptc.952G>A p.Val318Met missense_variant 9/9
ELOVL5NM_001301856.2 linkuse as main transcriptc.871G>A p.Val291Met missense_variant 8/8
ELOVL5NM_001242830.2 linkuse as main transcriptc.746G>A p.Cys249Tyr missense_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ELOVL5ENST00000304434.11 linkuse as main transcriptc.871G>A p.Val291Met missense_variant 8/81 NM_021814.5 P1Q9NYP7-1
ELOVL5ENST00000542638.5 linkuse as main transcriptc.746G>A p.Cys249Tyr missense_variant 7/71
ELOVL5ENST00000370918.8 linkuse as main transcriptc.952G>A p.Val318Met missense_variant 9/92 Q9NYP7-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000329
AC:
50
AN:
152162
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.000263
AC:
66
AN:
251038
Hom.:
0
AF XY:
0.000295
AC XY:
40
AN XY:
135702
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.000435
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000335
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000337
AC:
492
AN:
1461638
Hom.:
0
Cov.:
31
AF XY:
0.000373
AC XY:
271
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000356
Gnomad4 OTH exome
AF:
0.000679
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000328
AC:
50
AN:
152280
Hom.:
1
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.000307
Hom.:
0
Bravo
AF:
0.000408
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.000698
AC:
6
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000231
AC:
28
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000356

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeNov 06, 2023This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 291 of the ELOVL5 protein (p.Val291Met). This variant is present in population databases (rs146646780, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ELOVL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 2070080). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine 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. -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023ELOVL5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.40
Cadd
Benign
20
Dann
Uncertain
1.0
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.080
T
MutationTaster
Benign
1.0
D;D;D;D
Sift4G
Benign
0.20
T
Vest4
0.27
MVP
0.082
ClinPred
0.0092
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs146646780; hg19: chr6-53133954; API