6-53269248-G-A

Position:

• chr6-53269248-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021814.5(ELOVL5):​c.779C>T​(p.Ser260Phe) 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. 12/20 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_021814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.49

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24869308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5	c.779C>T	p.Ser260Phe	missense_variant	8/8	ENST00000304434.11	NP_068586.1
ELOVL5	NM_001242828.2	c.860C>T	p.Ser287Phe	missense_variant	9/9		NP_001229757.1
ELOVL5	NM_001301856.2	c.779C>T	p.Ser260Phe	missense_variant	8/8		NP_001288785.1
ELOVL5	NM_001242830.2	c.654C>T	p.Leu218Leu	synonymous_variant	7/7		NP_001229759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000304434.11	c.779C>T	p.Ser260Phe	missense_variant	8/8	1	NM_021814.5	ENSP00000306640.6
ELOVL5	ENST00000542638.5	c.654C>T	p.Leu218Leu	synonymous_variant	7/7	1		ENSP00000440728.2
ELOVL5	ENST00000370918.8	c.860C>T	p.Ser287Phe	missense_variant	9/9	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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.860C>T (p.S287F) alteration is located in exon 9 (coding exon 8) of the ELOVL5 gene. This alteration results from a C to T substitution at nucleotide position 860, causing the serine (S) at amino acid position 287 to be replaced by a phenylalanine (F). 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	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	.;T
Eigen	Benign	0.059
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.097
Sift	Benign	0.034	.;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.0080	.;B
Vest4		0.27
MutPred		0.45		.;Loss of disorder (P = 0.0107);
MVP		0.33
ClinPred		0.78	D
GERP RS		5.2
Varity_R		0.30
gMVP		0.55

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: chr6-53134046; COSMIC: COSV58653492;