6-53270651-T-C

Position:

chr6-53270651-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_021814.5(ELOVL5):c.698A>G(p.Tyr233Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

ELOVL5
NM_021814.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 3.44

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=0.17183697).

BP6

Variant 6-53270651-T-C is Benign according to our data. Variant chr6-53270651-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210935.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr6-53270651-T-C is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5 linkuse as main transcript	c.698A>G	p.Tyr233Cys	missense_variant	7/8	ENST00000304434.11	NP_068586.1	Q9NYP7-1A0A024RD35
ELOVL5	NM_001242828.2 linkuse as main transcript	c.779A>G	p.Tyr260Cys	missense_variant	8/9		NP_001229757.1	Q9NYP7-2
ELOVL5	NM_001301856.2 linkuse as main transcript	c.698A>G	p.Tyr233Cys	missense_variant	7/8		NP_001288785.1	Q9NYP7-1A0A024RD35B3KWH9
ELOVL5	NM_001242830.2 linkuse as main transcript	c.573A>G	p.Val191Val	synonymous_variant	6/7		NP_001229759.1	Q9NYP7A0A0A0MTI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELOVL5	ENST00000304434.11 linkuse as main transcript	c.698A>G	p.Tyr233Cys	missense_variant	7/8	1	NM_021814.5	ENSP00000306640.6	Q9NYP7-1
ELOVL5	ENST00000542638.5 linkuse as main transcript	c.573A>G	p.Val191Val	synonymous_variant	6/7	1		ENSP00000440728.2	A0A0A0MTI6
ELOVL5	ENST00000370918.8 linkuse as main transcript	c.779A>G	p.Tyr260Cys	missense_variant	8/9	2		ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000617

AC:

155

AN:

251284

Hom.:

AF XY:

0.000604

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00108

AC:

1572

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

791

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000630

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000958

Hom.:

Bravo

AF:

0.000555

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.00153

EpiControl

AF:

0.00142

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 07, 2015

- -

Spinocerebellar ataxia type 38

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Knight Diagnostic Laboratories, Oregon Health and Sciences University

Nov 18, 2019

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.5

.;D

REVEL

Benign

0.29

Sift

Uncertain

0.011

.;D

Sift4G

Uncertain

0.052

T;T

Polyphen

0.90

.;P

Vest4

0.77

MVP

0.34

ClinPred

0.15

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.81

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