Variant 10-102229124-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152310.3(ELOVL3):c.685T>C(p.Cys229Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,614,010 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

ELOVL3
NM_152310.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Variant links:

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]

ELOVL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL3	NM_152310.3 linkuse as main transcript	c.685T>C	p.Cys229Arg	missense_variant	4/4	ENST00000370005.4	NP_689523.1
ELOVL3	XM_011540245.2 linkuse as main transcript	c.685T>C	p.Cys229Arg	missense_variant	5/5		XP_011538547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL3	ENST00000370005.4 linkuse as main transcript	c.685T>C	p.Cys229Arg	missense_variant	4/4	1	NM_152310.3	ENSP00000359022	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251228

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.685T>C (p.C229R) alteration is located in exon 4 (coding exon 4) of the ELOVL3 gene. This alteration results from a T to C substitution at nucleotide position 685, causing the cysteine (C) at amino acid position 229 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

0.97

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.095

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.58

MutPred

0.77

Gain of disorder (P = 0.002);

MVP

0.60

MPC

1.4

ClinPred

1.0

GERP RS

5.8

Varity_R

0.96

gMVP

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over