6-53269450-CTTTT-CTTT

Variant names:

• chr6-53269450-CT-C
• rs3215545
• NM_021814.5:c.757-181delA

Variant summary

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

The NM_021814.5(ELOVL5):​c.757-181delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 147,122 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00040 (0 hom., cov: 32)
• Consequence: ELOVL5 NM_021814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021814.5. 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.757-181delA		intron	N/A	NP_068586.1	Q9NYP7-1
	ELOVL5	NM_001242828.2		c.838-181delA		intron	N/A	NP_001229757.1	Q9NYP7-2
	ELOVL5	NM_001301856.2		c.757-181delA		intron	N/A	NP_001288785.1	Q9NYP7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL5	ENST00000304434.11	TSL:1 MANE Select	c.757-181delA		intron	N/A	ENSP00000306640.6	Q9NYP7-1
	ELOVL5	ENST00000542638.5	TSL:1	c.632-181delA		intron	N/A	ENSP00000440728.2	A0A0A0MTI6
	ELOVL5	ENST00000370918.8	TSL:2	c.838-181delA		intron	N/A	ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 59 AN: 147064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000409

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000787

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000332

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000401 AC: 59 AN: 147122 Hom.: 0 Cov.: 32 AF XY: 0.000447 AC XY: 32 AN XY: 71668

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000247 AC: 10 AN: 40448

American (AMR) AF: 0.000408 AC: 6 AN: 14700

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3402

East Asian (EAS) AF: 0.000790 AC: 4 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4670

European-Finnish (FIN) AF: 0.00170 AC: 16 AN: 9408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000332 AC: 22 AN: 66242

Other (OTH) AF: 0.00 AC: 0 AN: 1994

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3215545; hg19: chr6-53134248;