6-53270647-G-T

Position:

• chr6-53270647-G-T

Variant summary

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

The NM_021814.5(ELOVL5):​c.702C>A​(p.Phe234Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.87

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	Protein	UniProt
ELOVL5	NM_021814.5	c.702C>A	p.Phe234Leu	missense_variant	7/8	ENST00000304434.11	NP_068586.1
ELOVL5	NM_001242828.2	c.783C>A	p.Phe261Leu	missense_variant	8/9		NP_001229757.1
ELOVL5	NM_001301856.2	c.702C>A	p.Phe234Leu	missense_variant	7/8		NP_001288785.1
ELOVL5	NM_001242830.2	c.577C>A	p.Pro193Thr	missense_variant	6/7		NP_001229759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000304434.11	c.702C>A	p.Phe234Leu	missense_variant	7/8	1	NM_021814.5	ENSP00000306640.6
ELOVL5	ENST00000542638.5	c.577C>A	p.Pro193Thr	missense_variant	6/7	1		ENSP00000440728.2
ELOVL5	ENST00000370918.8	c.783C>A	p.Phe261Leu	missense_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

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Jun 21, 2022

PM2_SUP -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.7	.;N
REVEL	Benign	0.15
Sift	Benign	0.14	.;T
Sift4G	Benign	0.23	T;T
Polyphen		0.22	.;B
Vest4		0.73
MutPred		0.58		.;Loss of catalytic residue at F234 (P = 0.4511);
MVP		0.69
ClinPred		0.83	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1561860638; hg19: chr6-53135445;