6-53270655-A-G

Position:

• chr6-53270655-A-G

Variant summary

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

The NM_001242830.2(ELOVL5):​c.569T>C​(p.Val190Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELOVL5 NM_001242830.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.775

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=0.06737667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5	c.694T>C	p.Leu232Leu	synonymous_variant	7/8	ENST00000304434.11	NP_068586.1
ELOVL5	NM_001242830.2	c.569T>C	p.Val190Ala	missense_variant	6/7		NP_001229759.1
ELOVL5	NM_001242828.2	c.775T>C	p.Leu259Leu	synonymous_variant	8/9		NP_001229757.1
ELOVL5	NM_001301856.2	c.694T>C	p.Leu232Leu	synonymous_variant	7/8		NP_001288785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000542638.5	c.569T>C	p.Val190Ala	missense_variant	6/7	1		ENSP00000440728.2
ELOVL5	ENST00000304434.11	c.694T>C	p.Leu232Leu	synonymous_variant	7/8	1	NM_021814.5	ENSP00000306640.6
ELOVL5	ENST00000370918.8	c.775T>C	p.Leu259Leu	synonymous_variant	8/9	2		ENSP00000359956.5

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

Revvity Omics, Revvity

Oct 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.4
DANN	Benign	0.75
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.067	T
Sift4G	Benign	0.60	T
Vest4		0.22
MVP		0.25
GERP RS		-0.025
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr6-53135453;