Variant 11-58834465-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000287275.6(GLYATL2):c.849G>T(p.Trp283Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,602,818 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W283R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GLYATL2
ENST00000287275.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

GLYATL2 (HGNC:24178): (glycine-N-acyltransferase like 2) Enables glycine N-acyltransferase activity. Involved in long-chain fatty acid catabolic process; medium-chain fatty acid catabolic process; and monounsaturated fatty acid catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GLYATL2	NM_145016.4 linkuse as main transcript	c.849G>T	p.Trp283Cys	missense_variant	6/6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3 linkuse as main transcript	c.849G>T	p.Trp283Cys	missense_variant	7/7		XP_016872826.1
GLYATL2	XM_017017338.3 linkuse as main transcript	c.849G>T	p.Trp283Cys	missense_variant	6/6		XP_016872827.1
GLYATL2	XM_047426545.1 linkuse as main transcript	c.726G>T	p.Trp242Cys	missense_variant	5/5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6 linkuse as main transcript	c.849G>T	p.Trp283Cys	missense_variant	6/6	1	NM_145016.4	ENSP00000287275	P1
GLYATL2	ENST00000532258.1 linkuse as main transcript	c.849G>T	p.Trp283Cys	missense_variant	7/7	1		ENSP00000434277	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1450714

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720886

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000302

Hom.:

Bravo

AF:

0.00000756

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

Oct 17, 2023

The c.849G>T (p.W283C) alteration is located in exon 6 (coding exon 5) of the GLYATL2 gene. This alteration results from a G to T substitution at nucleotide position 849, causing the tryptophan (W) at amino acid position 283 to be replaced by a cysteine (C). 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

0.91

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.0062

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.1

M;M

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-11

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.50

MutPred

0.85

Loss of ubiquitination at K287 (P = 0.0508);Loss of ubiquitination at K287 (P = 0.0508);

MVP

0.51

MPC

0.16

ClinPred

1.0

GERP RS

4.1

Varity_R

0.59

gMVP

0.51

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