chr10-102228461-T-C

Position:

• chr10-102228461-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_152310.3(ELOVL3):​c.278T>C​(p.Leu93Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ELOVL3 NM_152310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL3	NM_152310.3	c.278T>C	p.Leu93Pro	missense_variant	3/4	ENST00000370005.4	NP_689523.1
ELOVL3	XM_011540245.2	c.278T>C	p.Leu93Pro	missense_variant	4/5		XP_011538547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL3	ENST00000370005.4	c.278T>C	p.Leu93Pro	missense_variant	3/4	1	NM_152310.3	ENSP00000359022	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jan 02, 2024

The c.278T>C (p.L93P) alteration is located in exon 3 (coding exon 3) of the ELOVL3 gene. This alteration results from a T to C substitution at nucleotide position 278, causing the leucine (L) at amino acid position 93 to be replaced by a proline (P). 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	0.87
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	0.068
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.97	D
Vest4		0.72
MutPred		0.76		Loss of stability (P = 0.0466);
MVP		0.49
MPC		0.97
ClinPred		0.95	D
GERP RS		3.5
Varity_R		0.79
gMVP		0.89

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: chr10-103988218;