6-53269156-C-T

Position:

chr6-53269156-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

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]

ELOVL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.080304325).

BP6

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: {Uncertain_significance=1, Benign=1}.

BS2

High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant	8/8	ENST00000304434.11	NP_068586.1	Q9NYP7-1A0A024RD35
ELOVL5	NM_001242828.2 linkuse as main transcript	c.952G>A	p.Val318Met	missense_variant	9/9		NP_001229757.1	Q9NYP7-2
ELOVL5	NM_001301856.2 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant	8/8		NP_001288785.1	Q9NYP7-1A0A024RD35B3KWH9
ELOVL5	NM_001242830.2 linkuse as main transcript	c.746G>A	p.Cys249Tyr	missense_variant	7/7		NP_001229759.1	Q9NYP7A0A0A0MTI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELOVL5	ENST00000304434.11 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant	8/8	1	NM_021814.5	ENSP00000306640.6	Q9NYP7-1
ELOVL5	ENST00000542638.5 linkuse as main transcript	c.746G>A	p.Cys249Tyr	missense_variant	7/7	1		ENSP00000440728.2	A0A0A0MTI6
ELOVL5	ENST00000370918.8 linkuse as main transcript	c.952G>A	p.Val318Met	missense_variant	9/9	2		ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152162

Hom.:

Cov.:

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:

AN:

251038

Hom.:

AF XY:

0.000295

AC XY:

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.:

Cov.:

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

AF:

0.000328

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

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.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000866

AC:

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

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ELOVL5: BP4, BS1, BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 06, 2023	This 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.40

M_CAP

Benign

0.0085

MetaRNN

Benign

0.080

Sift4G

Benign

0.20

Vest4

0.27

MVP

0.082

ClinPred

0.0092

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.

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