rs41273880

chr6-53270651-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 3.44

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]

ACMG classification

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 GnomAd at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELOVL5	NM_021814.5	c.698A>G	p.Tyr233Cys	missense_variant	7/8	ENST00000304434.11
ELOVL5	NM_001242828.2	c.779A>G	p.Tyr260Cys	missense_variant	8/9
ELOVL5	NM_001301856.2	c.698A>G	p.Tyr233Cys	missense_variant	7/8
ELOVL5	NM_001242830.2	c.573A>G	p.Val191=	synonymous_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELOVL5	ENST00000304434.11	c.698A>G	p.Tyr233Cys	missense_variant	7/8	1	NM_021814.5	P1
ELOVL5	ENST00000542638.5	c.573A>G	p.Val191=	synonymous_variant	6/7	1
ELOVL5	ENST00000370918.8	c.779A>G	p.Tyr260Cys	missense_variant	8/9	2

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152152 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.000604 AC XY: 82 AN XY: 135808

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.: 1 Cov.: 31 AF XY: 0.00109 AC XY: 791 AN XY: 727234

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: 96 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74448

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.: 0

Bravo AF: 0.000555

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000486 AC: 59

EpiCase AF: 0.00153

EpiControl AF: 0.00142

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 07, 2015

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2023

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.56	T
REVEL	Benign	0.29
Sift4G	Uncertain	0.052	T;T
Polyphen		0.90	.;P
Vest4		0.77
MVP		0.34
ClinPred		0.15	T
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

Other links and lift over

dbSNP: rs41273880; hg19: chr6-53135449;