rs146646780

Variant summary

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

The NM_021814.5(ELOVL5):​c.871G>T​(p.Val291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V291M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ELOVL5
NM_021814.5 missense

Scores

2
10

Clinical Significance

Not reported in ClinVar

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]

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=0.13046601).
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ELOVL5NM_021814.5 linkc.871G>T p.Val291Leu missense_variant Exon 8 of 8 ENST00000304434.11 NP_068586.1 Q9NYP7-1A0A024RD35
ELOVL5NM_001242828.2 linkc.952G>T p.Val318Leu missense_variant Exon 9 of 9 NP_001229757.1 Q9NYP7-2
ELOVL5NM_001301856.2 linkc.871G>T p.Val291Leu missense_variant Exon 8 of 8 NP_001288785.1 Q9NYP7-1A0A024RD35B3KWH9
ELOVL5NM_001242830.2 linkc.746G>T p.Cys249Phe missense_variant Exon 7 of 7 NP_001229759.1 Q9NYP7A0A0A0MTI6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ELOVL5ENST00000304434.11 linkc.871G>T p.Val291Leu missense_variant Exon 8 of 8 1 NM_021814.5 ENSP00000306640.6 Q9NYP7-1
ELOVL5ENST00000542638.5 linkc.746G>T p.Cys249Phe missense_variant Exon 7 of 7 1 ENSP00000440728.2 A0A0A0MTI6
ELOVL5ENST00000370918.8 linkc.952G>T p.Val318Leu missense_variant Exon 9 of 9 2 ENSP00000359956.5 Q9NYP7-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
251038
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135702
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461638
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727120
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000162
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Uncertain
0.99
Eigen
Benign
0.0037
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.13
T
Sift4G
Benign
0.17
T
Vest4
0.25
MVP
0.043
ClinPred
0.19
T
GERP RS
6.0

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