4-110051754-T-C

Position:

• chr4-110051754-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_024090.3(ELOVL6):​c.382A>G​(p.Ile128Val) 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. 13/21 in silico tools predict 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: 6.50

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 1 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=0.16401845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELOVL6	NM_024090.3	c.382A>G	p.Ile128Val	missense_variant	4/4	ENST00000302274.8
ELOVL6	NM_001130721.2	c.382A>G	p.Ile128Val	missense_variant	5/5
ELOVL6	XM_011532233.4	c.382A>G	p.Ile128Val	missense_variant	5/5
ELOVL6	XM_011532234.4	c.382A>G	p.Ile128Val	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELOVL6	ENST00000302274.8	c.382A>G	p.Ile128Val	missense_variant	4/4	2	NM_024090.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 12, 2023

The c.382A>G (p.I128V) alteration is located in exon 4 (coding exon 4) of the ELOVL6 gene. This alteration results from a A to G substitution at nucleotide position 382, causing the isoleucine (I) at amino acid position 128 to be replaced by a valine (V). 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	0.067
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.41
DEOGEN2	Benign	0.022	T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.89	N;N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.14	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.65	T;T;T
Sift4G	Benign	0.97	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.28
MutPred		0.42		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.13
MPC		1.1
ClinPred		0.34	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
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: chr4-110972910;