6-53269254-C-T

Position:

• chr6-53269254-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021814.5(ELOVL5):​c.773G>A​(p.Gly258Glu) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELOVL5 NM_021814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05153328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5	c.773G>A	p.Gly258Glu	missense_variant	8/8	ENST00000304434.11	NP_068586.1
ELOVL5	NM_001242828.2	c.854G>A	p.Gly285Glu	missense_variant	9/9		NP_001229757.1
ELOVL5	NM_001301856.2	c.773G>A	p.Gly258Glu	missense_variant	8/8		NP_001288785.1
ELOVL5	NM_001242830.2	c.648G>A	p.Arg216Arg	synonymous_variant	7/7		NP_001229759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000304434.11	c.773G>A	p.Gly258Glu	missense_variant	8/8	1	NM_021814.5	ENSP00000306640.6
ELOVL5	ENST00000542638.5	c.648G>A	p.Arg216Arg	synonymous_variant	7/7	1		ENSP00000440728.2
ELOVL5	ENST00000370918.8	c.854G>A	p.Gly285Glu	missense_variant	9/9	2		ENSP00000359956.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457870 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725236

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.854G>A (p.G285E) alteration is located in exon 9 (coding exon 8) of the ELOVL5 gene. This alteration results from a G to A substitution at nucleotide position 854, causing the glycine (G) at amino acid position 285 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Benign	0.089	.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.030	.;N
REVEL	Benign	0.014
Sift	Benign	0.80	.;T
Sift4G	Benign	0.78	T;T
Polyphen		0.0	.;B
Vest4		0.087
MutPred		0.42		.;Gain of solvent accessibility (P = 0.024);
MVP		0.043
ClinPred		0.035	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-53134052;