10-102228889-C-A

Position:

• chr10-102228889-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152310.3(ELOVL3):​c.450C>A​(p.Ser150Arg) variant causes a missense change involving the alteration of a non-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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELOVL3 NM_152310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

Genes affected

ELOVL3 (HGNC:18047): (ELOVL fatty acid elongase 3) This gene encodes a protein that belongs to the GNS1/SUR4 family. Members of this family play a role in elongation of long chain fatty acids to provide precursors for synthesis of sphingolipids and ceramides. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL3	NM_152310.3	c.450C>A	p.Ser150Arg	missense_variant	4/4	ENST00000370005.4	NP_689523.1
ELOVL3	XM_011540245.2	c.450C>A	p.Ser150Arg	missense_variant	5/5		XP_011538547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL3	ENST00000370005.4	c.450C>A	p.Ser150Arg	missense_variant	4/4	1	NM_152310.3	ENSP00000359022	P1

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.450C>A (p.S150R) alteration is located in exon 4 (coding exon 4) of the ELOVL3 gene. This alteration results from a C to A substitution at nucleotide position 450, causing the serine (S) at amino acid position 150 to be replaced by an arginine (R). 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	Pathogenic	0.99
BayesDel_addAF	Benign	-0.0087	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	0.77	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.81		Loss of glycosylation at S150 (P = 0.0289);
MVP		0.53
MPC		1.1
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.31
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr10-103988646;