6-53269224-T-C

Position:

chr6-53269224-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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

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]

ELOVL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

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

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5 linkuse as main transcript	c.803A>G	p.Asp268Gly	missense_variant	8/8	ENST00000304434.11	NP_068586.1	Q9NYP7-1A0A024RD35
ELOVL5	NM_001242828.2 linkuse as main transcript	c.884A>G	p.Asp295Gly	missense_variant	9/9		NP_001229757.1	Q9NYP7-2
ELOVL5	NM_001301856.2 linkuse as main transcript	c.803A>G	p.Asp268Gly	missense_variant	8/8		NP_001288785.1	Q9NYP7-1A0A024RD35B3KWH9
ELOVL5	NM_001242830.2 linkuse as main transcript	c.678A>G	p.Gly226Gly	synonymous_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.803A>G	p.Asp268Gly	missense_variant	8/8	1	NM_021814.5	ENSP00000306640.6	Q9NYP7-1
ELOVL5	ENST00000542638.5 linkuse as main transcript	c.678A>G	p.Gly226Gly	synonymous_variant	7/7	1		ENSP00000440728.2	A0A0A0MTI6
ELOVL5	ENST00000370918.8 linkuse as main transcript	c.884A>G	p.Asp295Gly	missense_variant	9/9	2		ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249470

Hom.:

AF XY:

0.0000148

AC XY:

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:

AN:

1461120

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

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.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 07, 2022

This 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

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.072

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.52

.;N

REVEL

Benign

0.029

Sift

Benign

0.30

.;T

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

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.

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