rs587777670

Variant names:

• chr6-53270660-C-A
• rs587777670
• NM_021814.5:c.689G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-53270660-C-A
• chr6-53270660-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001242828.2(ELOVL5):​c.770G>T​(p.Gly257Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELOVL5 NM_001242828.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.90
• Publications: 8 publications found

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]

ELOVL5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 38

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911
• PP5: Variant 6-53270660-C-A is Pathogenic according to our data. Variant chr6-53270660-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 144075.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242828.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL5	NM_021814.5	MANE Select	c.689G>T	p.Gly230Val	missense	Exon 7 of 8	NP_068586.1
	ELOVL5	NM_001242828.2		c.770G>T	p.Gly257Val	missense	Exon 8 of 9	NP_001229757.1
	ELOVL5	NM_001301856.2		c.689G>T	p.Gly230Val	missense	Exon 7 of 8	NP_001288785.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL5	ENST00000304434.11	TSL:1 MANE Select	c.689G>T	p.Gly230Val	missense	Exon 7 of 8	ENSP00000306640.6
	ELOVL5	ENST00000542638.5	TSL:1	c.564G>T	p.Trp188Cys	missense	Exon 6 of 7	ENSP00000440728.2
	ELOVL5	ENST00000370918.8	TSL:2	c.770G>T	p.Gly257Val	missense	Exon 8 of 9	ENSP00000359956.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spinocerebellar ataxia type 38 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-1.2	T
PhyloP100		7.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.1	D
REVEL	Pathogenic	0.76
Sift	Benign	0.051	T
Sift4G	Benign	0.082	T
Polyphen		0.98	D
Vest4		0.92
MutPred		0.64		Loss of helix (P = 0.2271)
MVP		0.52
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.81
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -17

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

Other links and lift over

dbSNP: rs587777670; hg19: chr6-53135458;