dbSNP rs765835685: ELOVL5:p.Gly258Val (chr6-53269254-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021814.5(ELOVL5):c.773G>T(p.Gly258Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. G258E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ELOVL5
NM_021814.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 38
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ELOVL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09140223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021814.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELOVL5	NM_021814.5	MANE Select	c.773G>T	p.Gly258Val	missense	Exon 8 of 8	NP_068586.1	Q9NYP7-1
ELOVL5	NM_001242828.2		c.854G>T	p.Gly285Val	missense	Exon 9 of 9	NP_001229757.1	Q9NYP7-2
ELOVL5	NM_001301856.2		c.773G>T	p.Gly258Val	missense	Exon 8 of 8	NP_001288785.1	Q9NYP7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELOVL5	ENST00000304434.11	TSL:1 MANE Select	c.773G>T	p.Gly258Val	missense	Exon 8 of 8	ENSP00000306640.6	Q9NYP7-1
ELOVL5	ENST00000542638.5	TSL:1	c.648G>T	p.Arg216Ser	missense	Exon 7 of 7	ENSP00000440728.2	A0A0A0MTI6
ELOVL5	ENST00000370918.8	TSL:2	c.854G>T	p.Gly285Val	missense	Exon 9 of 9	ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

245274

AF XY:

0.00000753

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33238

American (AMR)

AF:

0.00

AC:

AN:

44112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.00

AC:

AN:

85648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109994

Other (OTH)

AF:

0.00

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.14

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.011

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

PhyloP100

2.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.026

Sift

Benign

0.22

Sift4G

Benign

0.27

Polyphen

0.0060

Vest4

0.16

MutPred

0.50

Loss of disorder (P = 0.0325)

MVP

0.11

ClinPred

0.081

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.45

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over