4-110051427-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_024090.3(ELOVL6):c.709C>T(p.Leu237Phe) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELOVL6 NM_024090.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

ELOVL6 (HGNC:15829): (ELOVL fatty acid elongase 6) Fatty acid elongases (EC 6.2.1.3), such as ELOVL6, use malonyl-CoA as a 2-carbon donor in the first and rate-limiting step of fatty acid elongation (Moon et al., 2001 [PubMed 11567032]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ELOVL6
• BP4: Computational evidence support a benign effect (MetaRNN=0.2986672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELOVL6	NM_024090.3	c.709C>T	p.Leu237Phe	missense_variant	4/4	ENST00000302274.8
ELOVL6	NM_001130721.2	c.709C>T	p.Leu237Phe	missense_variant	5/5
ELOVL6	XM_011532233.4	c.709C>T	p.Leu237Phe	missense_variant	5/5
ELOVL6	XM_011532234.4	c.709C>T	p.Leu237Phe	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELOVL6	ENST00000302274.8	c.709C>T	p.Leu237Phe	missense_variant	4/4	2	NM_024090.3	P1
ELOVL6	ENST00000394607.7	c.709C>T	p.Leu237Phe	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251154 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135714

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2022

The c.709C>T (p.L237F) alteration is located in exon 4 (coding exon 4) of the ELOVL6 gene. This alteration results from a C to T substitution at nucleotide position 709, causing the leucine (L) at amino acid position 237 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	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	0.078
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.20
Sift	Benign	0.035	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.0050	B;B
Vest4		0.58
MVP		0.33
MPC		1.5
ClinPred		0.67	D
GERP RS		5.2
Varity_R		0.24
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs375827628; hg19: chr4-110972583;