6-53270657-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021814.5(ELOVL5):c.692G>T(p.Trp231Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELOVL5 NM_021814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELOVL5	NM_021814.5	c.692G>T	p.Trp231Leu	missense_variant	7/8	ENST00000304434.11
ELOVL5	NM_001242828.2	c.773G>T	p.Trp258Leu	missense_variant	8/9
ELOVL5	NM_001301856.2	c.692G>T	p.Trp231Leu	missense_variant	7/8
ELOVL5	NM_001242830.2	c.567G>T	p.Leu189Phe	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELOVL5	ENST00000304434.11	c.692G>T	p.Trp231Leu	missense_variant	7/8	1	NM_021814.5	P1
ELOVL5	ENST00000542638.5	c.567G>T	p.Leu189Phe	missense_variant	6/7	1
ELOVL5	ENST00000370918.8	c.773G>T	p.Trp258Leu	missense_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 38 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

3billion

Sep 01, 2022

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.040
Cadd	Uncertain	24
Dann	Uncertain	0.98
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.25	T
MutationTaster	Benign	1.0	D;D;D;D
Sift4G	Uncertain	0.0060	D
Vest4		0.29
MVP		0.24
ClinPred		0.81	D
GERP RS		6.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: -14

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: chr6-53135455;