dbSNP rs587777671: ELOVL5:p.Leu72Val (chr6-53291808-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_021814.5(ELOVL5):c.214C>G(p.Leu72Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELOVL5
NM_021814.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.30

Publications

6 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ELOVL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 6-53291808-G-C is Pathogenic according to our data. Variant chr6-53291808-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 144076.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELOVL5	NM_021814.5 link	c.214C>G	p.Leu72Val	missense_variant	Exon 3 of 8	ENST00000304434.11	NP_068586.1	Q9NYP7-1A0A024RD35
ELOVL5	NM_001242828.2 link	c.214C>G	p.Leu72Val	missense_variant	Exon 3 of 9		NP_001229757.1	Q9NYP7-2
ELOVL5	NM_001301856.2 link	c.214C>G	p.Leu72Val	missense_variant	Exon 3 of 8		NP_001288785.1	Q9NYP7-1A0A024RD35B3KWH9
ELOVL5	NM_001242830.2 link	c.214C>G	p.Leu72Val	missense_variant	Exon 3 of 7		NP_001229759.1	Q9NYP7A0A0A0MTI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000304434.11 link	c.214C>G	p.Leu72Val	missense_variant	Exon 3 of 8	1	NM_021814.5	ENSP00000306640.6		Q9NYP7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111764

Other (OTH)

AF:

0.00

AC:

AN:

60362

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 38

Pathogenic:1Other:1

Aug 07, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;.;T

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.84

L;.;L

PhyloP100

4.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.86

.;N;N

REVEL

Pathogenic

0.67

Sift

Benign

0.19

.;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.16

.;.;B

Vest4

0.74

MutPred

0.77

Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);

MVP

0.093

ClinPred

0.74

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.71

Mutation Taster

=5/95

disease causing (ClinVar)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over